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Biomedical subjects

D S Postma

Publications and source records attributed to D S Postma.

At least 91 records · Page 5Linked to original sources
PubMed2001

Treatment of asthma by the inhaled corticosteroid ciclesonide given either in the morning or evening.

The study addressed the question whether the novel inhaled prodrug corticosteroid ciclesonide is equally effective when inhaled in the morning compared to the evening. For this purpose a double-blind, randomized, parallel group study was initiated in which 209 asthmatic patients (forced expiratory volume in one second = 50-90% predicted) inhaled either 200 microg ciclesonide in the morning or in the evening, for 8 weeks. Efficacy was assessed by means of spirometry as well as daily recordings of morning and evening peak expiratory flow (PEF), symptoms and use of rescue medication. The 24-h urinary cortisol excretion was measured to evaluate any effect on hypothalamic-pituitary-adrenol axis. Ciclesonide significantly improved asthma control. Morning and evening administration was shown to be equally effective for the different spirometry variables, evening PEF, symptoms, use of rescue medication and number of asthma exacerbations. Regarding morning PEF, the improvements after evening dosing were more prominent and equivalence of morning and evening administration could not be demonstrated. No relevant influence on cortisol excretion was found. Overall, the study indicates that ciclesonide can be given either in the morning or in the evening to meet the patients' preference and individual medical needs, although evening administration may lead to a more pronounced improvement in morning peak expiratory flow.

Administration, Inhalation↗
PubMed2001

L-Arginine is not the limiting factor for nitric oxide synthesis by human alveolar macrophages in vitro.

Unlike murine mononuclear phagocytes, human macrophages do not release high amounts of nitric oxide (NO) in vitro despite the presence of nitric oxide synthase (NOS). To determine whether this limited NO synthesis in vitro is due to limited availability of the NOS substrate L-arginine, and putative NOS inhibiting factors present in foetal serum preparations, both alveolar macrophages (AM) and monocyte derived macrophages (MDM) were incubated in various circumstances. Nitrite production measured using stimulated AM was typically <5 pmol x min(-1) x 10(-6) cells. A range of stimuli were tested, but without result. Furthermore, incubation of MDMs with normal human serum or purified bovine serum albumin instead of foetal calf serum failed to enhance NO production. Moreover, neither the use of arginase inhibitors nor the addition of surplus L-arginine resulted in an increased NO synthesis. Interestingly, addition of the NOS intermediate Nomega-hydroxy-L-arginine (100 microM) to AM led to nitrite release, which was unaffected by the NOS inhibitor amino guanidine showing that this effect is NOS independent. It is concluded that the limited nitric oxide production of human macrophages in vitro can neither be explained by limited availability of L-arginine, nor by nitric oxide synthase inhibiting substances in foetal serum. Furthermore, it is shown that nitrite release from Nomega-hydroxy-L-arginine by alveolar macrophages is nitric oxide synthase independent.

Animals↗
PubMed2001

The feasibility of airways hyperresponsiveness as an inclusion criterion for studies on childhood asthma.

The feasibility of moderately severe airway hyperresponsiveness (AH) was examined as an inclusion criterion for clinical trials in asthmatic children. During the baseline period of a long-term clinical trial in asthmatic children, maintenance therapy with fluticasone (200 microg x day(-1)) was stopped for a maximum of 8 weeks and methacholine challenges were performed at 2-week intervals or earlier if the patients' condition deteriorated. Patients were eligible to continue the study if the provocative dose of methacholine causing a 20% fall in forced expired volume in one second (FEV1) (PD20) was <80 microg. Fifty-one per cent of the children did not develop a PD20 < 80 microg after withdrawal of fluticasone. Patients with or without a PD20 <80 microg did not differ in duration of asthma, duration of treatment, or peak flow variation. Patients with a PD20 <80 microg had higher levels of total and specific immunoglobulin-E, and lower levels of FEV1 and mean maximal expiratory flow than patients with a PD20 > or = 80 microg. Forty-four per cent of the patients with a PD20 > or = 80 microg did not have any symptoms during the wash-out period and 39% of these patients remained free from symptoms during one year follow-up. The results of this study suggest that recruiting asthmatic children for clinical trials may be difficult if airways hyperresponsiveness is used as the sole inclusion criterion.

Androstadienes↗
PubMed2000

Histamine airway hyper-responsiveness and mortality from chronic obstructive pulmonary disease: a cohort study.

BACKGROUND: Smoking and airway lability, which is expressed by histamine airway hyper-responsiveness, are known risk factors for development of respiratory symptoms. Smoking is also associated with increased mortality risks. We studied whether airway hyper-responsiveness is associated with increased mortality, and whether this risk was independent of smoking and reduced lung function. METHODS: We followed up 2008 inhabitants of the communities of Vlagtwedde, Vlaardingen, and Meppel (Netherlands), who had histamine challenge test data, from 1964-72 for 30 years. Follow-up was 99% successful (29 patients lost to follow-up) with 1453 participants alive and 526 deaths (246 died from cardiovascular disease, 54 from lung cancer, and 21 from chronic obstructive pulmonary disease [COPD]). FINDINGS: Mortality from COPD increased with more severe hyper-responsiveness; relative risks of 3.83 (95% CI 0.97-15.1), 4.40 (1.16-16.7), 4.78 (1.27-18.0), 6.69 (1.71-26.1), and 15.8 (3.72-67.1) were associated with histamine thresholds of 32 g/L, 16 g/L, 8 g/L, 4 g/L, and 1 g/L, respectively, compared with no hyper-responsiveness. These risks were adjusted for sex, age, smoking, lung function, body-mass index, positive skin tests, eosinophilia, asthma, and city of residence. INTERPRETATION: Increased histamine airway hyper-responsiveness predicts mortality from COPD. Although this trend was more pronounced in smokers, an increasing proportion of COPD deaths with increasing hyper-responsiveness was also present among individuals who had never smoked.

Adolescent↗
PubMed2000

Major genes regulating total serum immunoglobulin E levels in families with asthma.

Immunoglobulin E (IgE) has a major role in the pathogenesis of allergic disorders and asthma. Previous data from 92 families, each identified through a proband with asthma, showed evidence for two major genes regulating total serum IgE levels. One of these genes mapped to 5q31-33. In the current study, the segregation analysis was extended by the addition of 108 probands and their families, ascertained in the same manner. A mixed recessive model (i.e., major recessive gene and residual genetic effect) was the best-fitting and most-parsimonious one-locus model of the segregation analysis. A mixed two-major-gene model (i.e., two major genes and residual genetic effect) fit the data significantly better than did the mixed recessive one-major-gene model. The second gene modified the effect of the first recessive gene. Individuals with the genotype aaBB (homozygous high-risk allele at the first gene and homozygous low-risk allele at the second locus) had normal IgE levels (mean 23 IU/ml), and only individuals with genotypes aaBb and aabb had high IgE levels (mean 282 IU/ml). A genomewide screening was performed using variance-component analysis. Significant evidence for linkage was found for a novel locus at 7q, with a multipoint LOD score of 3. 36 (P=.00004). A LOD score of 3.65 (P=.00002) was obtained after genotyping additional markers in this region. Evidence for linkage was also found for two previously reported regions, 5q and 12q, with LOD scores of 2.73 (P=.0002) and 2.46 (P=.0004), respectively. These results suggest that several major genes, plus residual genetic effects, regulate total serum IgE levels.

Adolescent↗
PubMed2000

Exhaled nitric oxide in children measured by tidal breathing method: differences between asthmatics and nonasthmatic controls.

The single-breath maneuver used to measure nitric oxide (NO) in adults cannot be performed by young children. We, therefore, developed a method of measuring NO in mixed exhaled gas collected during tidal breathing. NO was measured in mixed exhaled gas during 5 min of tidal breathing in 113 children 4-14 years of age: 22 nonasthmatics, 21 asthmatic children not taking inhaled corticosteroids, and 70 asthmatic children using inhaled corticosteroids. Exhaled NO levels (median, range) were significantly lower in nonasthmatic controls (median, range: 7, 2-10 ppb) than in asthmatic children on inhaled corticosteroids (8, 3-25 ppb; 95% CI for difference in medians with those of controls, 0-4 ppb), and in those not on inhaled corticosteroids (13, 6-37, ppb; 95% CI for difference in medians, 5-17 ppb). Asthmatic children not using inhaled corticosteroids had significantly higher exhaled NO levels than asthmatic children using inhaled corticosteroids (95% CI for difference in medians, 3-10 ppb). The tidal breathing method is a useful and practical way of measuring exhaled NO levels in children regardless of their age.

Administration, Inhalation↗
PubMed2000

Increased vascular expression of iNOS at day but not at night in asthmatic subjects with increased nocturnal airway obstruction.

Nitric oxide production by endothelial cells may have important consequences for the development of airway inflammation as well as for airway obstruction. The present study investigated whether the expression of vascular inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in human bronchi differs between asthmatic and healthy subjects, and whether it shows a circadian rhythm, especially in subjects with increased nocturnal airway obstruction. Bronchial biopsy samples were taken at 16:00 and 04:00 h from 13 healthy and 25 asthmatic subjects, 18-45 yrs. Biopsy samples were snap-frozen and double-immunostained for iNOS and eNOS in combination with a common vascular antigen (CD31). The degree of immunopositivity was expressed as a percentage of CD31-positive vessels encountered in complete biopsy sections. Asthmatic subjects showed greater iNOS expression than healthy controls: 23+/-15 versus 7+/-17% (mean+/-SD) at 16:00 h (p<0.001) and 19+/-15 versus 8+/-11% at 04:00 h (p<0.05). Asthmatic subjects with a fall in forced expiratory volume in one second of >10% of the predicted value between 16:00 and 04:00 h showed greater iNOS expression at 16:00 than at 04:00 h: 32+/-16 versus 20+/-13% (p<0.05). eNOS expression did not differ between healthy controls and asthmatic patients, nor did it differ between 16:00 and 04:00 h. It is suggested that asthmatic subjects with increased nocturnal airway obstruction demonstrate increased activation of inducible nitric oxide synthase during the day. The resulting nitric oxide production might protect against airway obstruction during the day. However, at night, nitric oxide production is probably insufficient to counterbalance the bronchoconstricting forces.

Adolescent↗
PubMed2000

Borg scores before and after challenge with adenosine 5'-monophosphate and methacholine in subjects with COPD and asthma.

Dyspnoea differs between subjects with chronic obstructive pulmonary disease (COPD) and asthma, partly because the underlying mechanisms for bronchoconstriction differ. This study investigated the possible role of inflammation and the contribution of clinical variables on dyspnoea in subjects with COPD and asthma. Forty-eight smoking subjects with COPD and 21 nonsmoking subjects with asthma, were challenged with adenosine 5'-monophosphate (AMP) and methacholine. The Borg score was assessed before and after each challenge. Mean increases in Borg score (per percentage decrease in baseline forced expiratory volume in one second (FEV1)) were significantly smaller in COPD than in asthma (p<0.01), values being 0.055 and 0.045 in COPD and 0.122 and 0.093 in asthma respectively. This difference was largely due to the fact that one-third of the subjects with COPD did not increase their Borg score during bronchoconstriction. The increase in Borg tended to be larger during AMP than during methacholine challenge, both in asthma and COPD. Changes in Borg scores were explained by age in COPD and by the Borg score before AMP challenge in asthma. The authors conclude that perception of dyspnoea during adenosine 5'-monophosphate and methacholine induced bronchoconstriction is lower in chronic obstructive pulmonary disease than in asthma and that age contributes to this difference. As adenosine 5'-monophosphate is regarded as an indirect marker of airway inflammation, the results suggest that inflammation is not important because both groups showed similar responses on such provocations.

Adenosine Monophosphate↗
PubMed2000

Changes in peak expiratory flow indices as a proxy for changes in bronchial hyperresponsiveness. Dutch Chronic Non-Specific Lung Disease study group.

Guidelines for asthma management advocate home peak expiratory flow (PEF) monitoring. It is commonly stated that PEF variability is a good proxy of bronchial hyperresponsiveness (BHR), a hallmark of asthma. However, this has hardly been tested longitudinally, as required to monitor asthma. This study assesses which PEF index correlates best with BHR longitudinally and whether the correlation improves when correcting PEF values for the known nonlinearity of mini-Wright PEF meters. Every 6 months, for a period of 2 yrs, PEF diary cards were filled in and BHR to histamine was tested in 104 patients with BHR and reversible airways obstruction, who started treatment with bronchodilators with (n=33) or without (n=71) inhaled corticosteroids. Within each subject, PEF indices and BHR were correlated longitudinally. The highest median correlation coefficients were obtained in the group of patients using inhaled corticosteroids. The PEF indices providing the best correlation with BHR were: mean PEF bronchodilator response (rho=-0.50) and within-day variation (% mean or % maximum) (with postbronchodilator values, rho=-0.50; without postbronchodilator values, rho=-0.40). Using PEF data corrected for the nonlinearity of the PEF meters did not result in higher correlation coefficients. Since current guidelines on asthma management recommend only bronchodilators on demand, the most useful peak expiratory flow index for reflecting bronchial hyperresponsiveness longitudinally is mean within-day peak expiratory flow variation (% mean or % maximum) (without postbronchodilator values). Since the correlation coefficients are not very strong, the authors suggest that peak expiratory flow measurements are not used as a proxy for bronchial hyperresponsiveness longitudinally but as a measurement in its own right. The use of corrections of peak expiratory flows for the nonlinearity of mini-Wright peak expiratory flow meters does not improve the correlation between peak expiratory flow and bronchial hyperresponsiveness.

Administration, Inhalation↗
PubMed2000

Apocynin inhibits peroxynitrite formation by murine macrophages.

Peroxynitrite (ONOO(-)) the highly reactive coupling product of nitric oxide and superoxide, has been implicated in the pathogenesis of an increasing number of (inflammatory) diseases. At present, however, selective peroxynitrite antagonizing agents with therapeutic potential are not available. Therefore, the NADPH-oxidase inhibitor apocynin (4-hydroxy-3-methoxy-acetophenone) was tested for its ability to inhibit peroxynitrite formation in vitro The murine macrophage cell-line J774A.1, stimulated with IFNgamma/LPS, was used as a model. Conversion of 123-dihydrorhodamine (123-DHR) to its oxidation product 123-rhodamine was used to measure peroxynitrite production. Stimulated peroxynitrite formation could be completely inhibited by apocynin, by the superoxide scavenger TEMPO as well as by the nitric oxide synthase inhibitor aminoguanidine. Apocynin and aminoguanidine specifically inhibited superoxide and nitric oxide formation respectively as confirmed by measuring lucigenin enhanced chemiluminescence and nitrite accumulation. It is concluded that J774A.1 macrophages produce significant amounts of peroxynitrite, which is associated with nitric oxide production and NADPH-oxidase dependent superoxide formation. The NADPH-oxidase inhibitor apocynin proved to be a potent inhibitor of both superoxide and peroxynitrite formation by macrophages, which may be of future therapeutic significance in a wide range of inflammatory disorders.

Acetophenones↗
PubMed2000

Airway inflammation and hyperresponsiveness to adenosine 5'-monophosphate in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often accompanied by bronchial hyperresponsiveness (BHR). Measurement of BHR may give information about airway inflammation. OBJECTIVE: To investigate the role of airway inflammation in hyperresponsiveness to adenosine 5'-monophosphate (AMP) in COPD. METHODS: We investigated inflammatory indices in induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies in subjects with COPD with and without hyperresponsiveness to AMP. Twelve nonatopic subjects with COPD with hyperresponsiveness to AMP (mean +/- SD, age 63 +/- 8 years, FEV1% predicted 56 +/- 13%), six without BHR (age 60 +/- 6 years, FEV1% predicted 65 +/- 11%) and 11 healthy nonatopic controls without BHR (age 58 +/- 8 years, FEV1% predicted 104 +/- 11%) participated in the study. RESULTS: Subjects with COPD with BHR had significantly higher numbers of mucosal CD8 + and higher percentages of sputum eosinophils than those without BHR (median, 550 cells/mm2; range, 30-1340 vs 280 cells/mm2; range, 110-450, P = 0.045; and median, 2.7%; range, 0.5-8.5 vs 0.6%; range, 0-0.8 %, P = 0.0036, respectively). No differences were observed in BAL fluid. CONCLUSION: We conclude that hyperresponsiveness to AMP in COPD is associated with airway inflammation that is characterized by increased numbers of mucosal CD8 + cells and percentages of sputum eosinophils. Hyperresponsiveness to AMP may be used as a marker of airway inflammation in COPD, but its significance in the clinical course remains to be determined.

Adenosine Monophosphate↗
PubMed2000

Asthma in adult patients presenting with symptoms of acute bronchitis in general practice.

OBJECTIVES: To investigate the association between asthma and acute bronchitis in adults and to ascertain criteria to help general practitioners (GPs) differentiate between acute bronchitis and asthma. DESIGN: Descriptive study. SETTING: Primary health care centre in The Netherlands. PATIENTS: 192 patients, aged 18-75 years, not known to have asthma or other pulmonary diseases, attending their GP with cough persisting for at least 2 weeks. METHODS: Patients were considered to have asthma or chronic obstructive pulmonary disease on the basis of a questionnaire on respiratory symptoms, spirometry and methacholine challenge testing. They were classified as having acute bronchitis if, according to international guidelines, coughing was more frequent than normal for at least 2 weeks, but no more than 4 weeks. Furthermore, either expectoration of purulent sputum for a maximum of 2 weeks and/or rhonchi as assessed by auscultation had to be present. By means of logistic regression symptoms, signs and peak expiratory flow measurements were sought to predict which patients with acute bronchitis actually had asthma. RESULTS: Of the 80 (41.7%) subjects with symptoms of acute bronchitis, 29 (36.9%) were patients with asthma. Within the acute bronchitis group, female sex and symptoms of current reported wheeze, reported episodes of attacks of dyspnoea over the last year and symptoms elicited by allergens were of help in identifying patients who actually had asthma. CONCLUSIONS: A considerable proportion of the patients presenting with acute bronchitis are actually patients with asthma. The absence or presence of a few symptoms and female sex may help to differentiate between these disorders.

Adult↗
PubMed2000

Eosinophilia is associated with increased all-cause mortality after a follow-up of 30 years in a general population sample.

We investigated whether allergy is associated with increased all-cause mortality. Two allergy markers, peripheral blood eosinophilia (> or =275 eosinophilic cells per mm3) and positive skin tests (sum score > or =3), were available for 5,383 subjects of a cohort study on asthma and chronic obstructive pulmonary disease in general population samples of Vlagtwedde and Vlaardingen, the Netherlands, in 1965-1972. During 30 years of follow-up, 1,135 subjects died. In a Cox regression analysis, eosinophilia was associated with an increased risk (relative risk = 1.4; 95% confidence interval = 1.2-1.7) of all-cause mortality, independent of gender, age, smoking habits, percentage predicted forced expiratory volume in 1 second (FEV1 % predicted), and positive skin tests at the start of the study. Subjects with positive skin tests had only an increased risk of all-cause mortality in the subgroup of subjects with FEV1 <80% of predicted (relative risk = 1.7; 95% confidence interval = 1.0-2.8). These results remained essentially unchanged after exclusion of subjects with asthma. We conclude that eosinophilia is associated with increased all-cause mortality. An increased number of peripheral blood eosinophils may reflect an increased inflammatory response, resulting in tissue injury. It is possible that the association between a low FEV1% predicted and all-cause mortality is partly mediated by an atopic constitution.

Adolescent↗
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

Bronchiolitis obliterans syndrome after lung transplantation and health-related quality of life.

The present study was undertaken to assess the relationship between health-related quality of life (HRQOL) and bronchiolitis obliterans syndrome (BOS), as both represent important parameters of outcome after lung transplantation. HRQOL was measured both cross-sectionally and longitudinally by standardized patient self-administered questionnaires, including the Nottingham Health Profile, the State-trait Anxiety Inventory, the Zung Self-Rating Depression Scale, and the Index of Well-Being. Data were collected at 4 and 7 mo, and every 6 mo afterwards for as long as 49 mo post-transplantation. The number of patients who completed the questionnaires varied from 72 at 4 mo, to 27 at 49 mo after transplantation. Cross-sectionally, the patients with BOS reported persistently statistically significantly more restrictions on the dimensions energy and physical mobility of the Nottingham Health Profile compared with patients without BOS. Other domains, i.e., pain, sleep, social interaction, and emotional reactions, were not affected. Additionally, patients with BOS reported statistically significantly more depressive symptoms and anxiety 1 and 2 yr after transplantation. Results from the longitudinal analysis support these findings, although no change in depressive symptoms could be found after onset of BOS. This study suggests that all lung transplant recipients improve in HRQOL. The development of BOS, however, is associated with a significantly reduced HRQOL.

Activities of Daily Living↗
PubMed2000

Effects of budesonide and formoterol on eosinophil activation induced by human lung fibroblasts.

Budesonide and formoterol are extensively used in current asthma therapy. Budesonide is known as potent antiinflammatory agent and formoterol also appears to have some antiinflammatory properties. We investigated inhibitory effects of these drugs on eosinophil activation in vitro as induced by fibroblast-conditioned medium (FCM). We measured the modulation of expression of clonal designator (CD)11b and L-selectin with flow cytometry after 4 h or 16 h of culture of eosinophils when budesonide or formoterol was applied either directly to the eosinophils while they were stimulated with FCM (direct method) or when each drug was applied to lung fibroblasts from which conditioned medium was then administered to eosinophils (indirect method). In the direct method, budesonide (10(-)(8) M) inhibited the modulation of CD11b (44 [25th to 75th percentiles: 26 to 66]% of control) and L-selectin (30 [-13 to 48]% of control) only after 16 h, and not after 4 h. Formoterol did not directly inhibit the modulation of eosinophil CD11b and L-selectin expression. In the indirect method, both budesonide and formoterol inhibited lung fibroblast activation, resulting in diminished eosinophil activation after 4 h. Budesonide or formoterol at 10(-)(8) M inhibited upregulation of CD11b to 26 [15 to 40]% and 38 [23 to 46]%, respectively, and inhibited L-selectin shedding to 14 [-3 to 50]% and 27 [2 to 62]%, respectively, of control values. These results show that budesonide inhibits eosinophil activation primarily through effects on lung fibroblasts, presumably by inhibiting production of granulocyte-macrophage colony-stimulating factor. After longer incubation periods, budesonide also directly inhibits eosinophil activation. In contrast, formoterol can inhibit eosinophil activation only via inhibitory effects on lung fibroblasts. We did not observe an additional effect of formoterol, beyond the effects induced by budesonide under any circumstance studied. Lung fibroblasts, in addition to eosinophils, may serve as important target cells for antiinflammatory treatment in asthma.

Adult↗
PubMed2000

Eosinophilic granulocytes and interleukin-6 level in bronchoalveolar lavage fluid are associated with the development of obliterative bronchiolitis after lung transplantation.

In a prospective cohort study, we assessed whether changes in total cell counts and differentiation and interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) concentrations in bronchoalveolar lavage fluid (BALF) are associated with a higher risk to develop obliterative bronchiolitis (OB). We investigated 60 lung transplant patients (follow-up of 2 to 8 yr) with either histologic evidence of OB within 1 yr after lung transplantation (n = 19) or no pathology, good outcome (GO) for at least 24 mo and well-preserved lung function, i.e., FEV > or = 80% of baseline (n = 41). Median time between lung transplantation and the first BAL was 42 d for the GO group and 41 d for the OB group (p > 0.05). In the bronchial fraction, median total cell counts (0.06 x 10(3)/ml versus 0.04 x 10(3)/ml), lymphocyte (9 x 10(3)/ml versus 2 x 10(3)/ml), and eosinophilic granulocyte counts (1 x 10(3)/ml versus 0) were significantly higher in the OB group than in the GO group (p < 0.05). In the alveolar fraction, this was the case for the median value of neutrophilic granulocyte counts (19 x 10(3)/ml versus 4 x 10(3)/ml), respectively. Median values of IL-6 and IL-8 concentrations in both bronchial (IL-6: 23 versus 6 pg/ml, IL-8: 744 versus 102 pg/ml) and alveolar fractions (IL-6: 13 versus 3 pg/ml, IL-8: 110 versus 30 pg/ml) of the BALF were significantly higher in the OB group than in the GO group. By means of logistic regression, we showed that higher total cell, neutrophilic granulocyte, and lymphocyte counts, the presence of eosinophilic granulocytes, and higher concentrations of IL-6 and IL-8 were significantly associated with an increased risk to develop OB. We conclude that monitoring cell counts, neutrophilic and eosinophilic granulocytes, IL-6, and IL-8 in BALF within 2 mo after lung transplantation in addition to the transbronchial lung biopsy (TBB) pathology will contribute to a better identification and management of the group of patients at risk for developing OB within a year.

Adult↗