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Biomedical subjects

L N Willems

Publications and source records attributed to L N Willems.

At least 19 recordsLinked to original sources
PubMed2000

Physical and psychological correlates of functioning in patients with chronic obstructive pulmonary disease.

We studied the contribution of coping and illness perceptions to outcome in patients with chronic obstructive pulmonary disease (COPD). In a longitudinal study, 64 patients completed the Medical Outcomes Study Instrument and the Illness Perception Questionnaire. Data on coping and severity of illness (spirometry) were also collected. Regression analyses showed that first-time illness perceptions and coping significantly contributed to the prediction of social functioning, mental health, health perceptions, total functioning score, and prediction of visits to the outpatient clinic and prescribed medication 1 year later. These results have important implications for the medical management of patients with COPD.

Adaptation, Psychological↗
PubMed1999

Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. The AMPUL Study Group.

According to international guidelines, the level and adjustment of antiinflammatory treatment for asthma are based solely on symptoms and lung function. We investigated whether a treatment strategy aimed at reducing airway hyperresponsiveness (AHR strategy) in addition to the recommendations in the existing guidelines (reference strategy) led to: (1) more effective control of asthma; and (2) greater improvement of chronic airways inflammation. To accomplish this, we conducted a randomized, prospective, parallel trial involving 75 adults with mild to moderate asthma who visited a clinic every 3 mo for 2 yr. At each visit, FEV1 and AHR to methacholine were assessed, and subjects kept diaries of symptoms, beta2-agonist use, and peak expiratory flow (PEF). Medication with corticosteroids (four levels) was adjusted according to a stepwise approach (reference strategy), to which four severity classes of AHR were added (AHR strategy). At entry and after 2 yr, bronchial biopsies were obtained by fiberoptic bronchoscopy. Patients treated according to the AHR strategy had a 1.8-fold lower rate of mild exacerbations than did patients in the reference strategy group (0. 23 and 0.43 exacerbation/yr/patient, respectively). FEV1 also improved to a significantly greater extent in the AHR strategy group (p </= 0.05). In bronchial biopsies this was accompanied by a greater reduction in thickness of the subepithelial reticular layer in the AHR strategy group than in the reference strategy group (mean difference [95% confidence interval (CI): 1.7 micrometers (0.2 to 3.1) micrometers]). The changes in AHR in both strategy groups were correlated with eosinophil counts in the biopsies (r = -0.48, p = 0.003). We conclude that reducing AHR in conjunction with optimizing symptoms and lung function leads to more effective control of asthma while alleviating chronic airways inflammation. This implies a role for the monitoring of AHR or other surrogate markers of inflammation in the long-term management of asthma.

Administration, Inhalation↗
PubMed1999

Compliance, hysteresis, and collapsibility of human small airways.

We tested the hypothesis that airway wall dimensions are important determinants for the mechanical properties of airways. Lung tissue was obtained from 31 smokers with different degrees of chronic obstructive pulmonary disease (COPD) who were operated on for a solitary lung lesion. Segments of small airways (n = 35) were mounted on cannulas in an organ bath and inflated and deflated cyclically between +15 and -15 cm H(2)O. For each airway this was done at baseline, after methacholine, and after isoprenaline. Specific compliance (sCdyn), specific hysteresis (seta), and pressure at which the airways collapsed (Pcol) were calculated from each recording. Airway wall dimensions were measured morphometrically. Lung function parameters of airflow obstruction were correlated to sCdyn, seta, and Pcol. At baseline, after methacholine, and after isoprenaline sCdyn was 0.059, 0.052, and 0. 085 cm H(2)O(-)(1), seta was 13.5, 12.9, and 7.1%, and Pcol was -3.4, -3.5, and -1.9 cm H(2)O, respectively. Differences between sCdyn, seta, and Pcol after methacholine and after isoprenaline were highly significant (p < 0.001). Of all dimensions studied, smooth muscle area, but not total wall area, was the most important determinant for sCdyn and for seta after methacholine. Specific hysteresis at baseline correlated to residual volume as a fraction of total lung capacity (RV/TLC) (r = 0.5, p = 0.05) and, in the presence of methacholine, to FEV(1)/FVC (r = -0.68, p = 0.02) and RV/TLC (r = 0. 5, p = 0.05). We conclude that, in this study, smooth muscle area and smooth muscle tone, but not total wall area, are determinants for compliance, hysteresis, and collapsibility of isolated airways obtained from smokers.

Adult↗
PubMed1998

Pretreatment serum lactate dehydrogenase as additional staging parameter in patients with small-cell lung carcinoma.

PURPOSE: At present the standard staging procedure in patients with small-cell lung cancer (SCLC) is extensive, expensive and time-consuming. Furthermore, the predictive and prognostic value of the current staging system is poor. To determine the value of pretreatment clinical and biochemical parameters to predict tumour stage and to assess prognosis, a retrospective study was performed of 121 consecutive patients with newly diagnosed SCLC. METHODS: On the basis of routine diagnostic procedures, 51 patients were staged as having limited disease and 70 patients as having extensive disease. During follow-up, data on tumour progression and survival were gathered. These data and the tumour stage were correlated with lactate dehydrogenase (LDH), alkaline phosphatase, liver enzymes, leucocyte count, protein, albumin, calcium, age and gender. RESULTS: Follow-up ranged from 1 week to 96 months, during which 110 patients died. In all patients with LDH levels above 400 U/l (n = 31), metastases were found at the initial stage, whereas all patients initially staged as having limited disease and LDH levels above 240 U/l showed tumour progression. Bone and liver were found to be the most commonly involved sites, whereas the incidence of brain metastases increased during follow-up. In patients initially staged as having limited disease, no differences in survival were found between those showing local recurrence and those developing metastases during follow-up (P = 0.67). Compared to the patients initially staged as having extensive disease, the survival of both groups was significantly better (P < 0.001). Significant independent variables of survival were LDH, albumin, initial stage and gender, but LDH was the best overall predictor (P < 0.001). CONCLUSION: These results suggest that pretreatment LDH may be used as an additional staging parameter in SCLC, which can identify prognostic subgroups before treatment.

Carcinoma, Small Cell↗
PubMed1998

Illness perceptions, coping and functioning in patients with rheumatoid arthritis, chronic obstructive pulmonary disease and psoriasis.

The present cross-sectional study analyzed the extent to which illness perceptions and coping strategies (as measured by the Illness Perception Questionnaire and the Utrecht Coping List, respectively) are associated with levels of daily functioning, as indicated by the Medical Outcomes Study SF-20, and disease-specific measures in 244 adults: 84 with rheumatoid arthritis (RA); 80 with chronic obstructive lung disease (COPD); and 80 with psoriasis. The results of stepwise regression analyses indicated that a strong illness identity, passive coping, belief in a long illness duration, belief in more severe consequences, and an unfavorable score on medical variables were associated with worse outcome on disease-specific measures of functioning and on general role and social functioning. Coping by seeking social support and beliefs in controllability/curability of the disease were significantly related to better functioning. The implications of these findings for future interventions and research are discussed.

Activities of Daily Living↗
PubMed1998

Pretreatment serum LDH as additional staging parameter in small-cell lung carcinoma.

BACKGROUND: In patients with limited disease staged small-cell lung cancer (SCLC), overall survival is still poor. Therefore, a retrospective study was carried out of 48 patients with limited disease staged SCLC to select a parameter which can identify prognostic subgroups at the time of diagnosis. MATERIALS AND METHODS: Follow-up varied from 3 to 96 months during which 38 patients died. Based on clinical outcome, patients were clustered into three groups: complete remission (CR) (n = 16); local recurrence (LOC) (n = 7); and distant recurrence (DIS) (n = 25). Age, gender and pretreatment biochemical parameters were correlated with clinical outcome and survival. RESULTS: No differences in survival were found in patients with LOC (14% 2-year survival) and DIS (16% 2-year survival) (P = 0.67). Patients with complete remission demonstrated a significantly better survival (75% 2-year survival). LDH was found to be the only significant correlate of both tumour progression and survival. All patients with pretreatment LDH levels > 240 IU/l (n = 13) demonstrated tumour recurrence. The survival rate of patients with LDH levels < 240 IU/l (41% 2-year survival) was much better than that of patients with LDH levels > 240 IU/l (8% 2-year survival) (P = 0.0001). CONCLUSION: LDH may be used for the identification of prognostic subgroups in limited disease SCLC. Patients showing pretreatment LDH levels > 240 IU/l have an extremely high risk of tumour recurrence, whereas survival is poor. In patients with LDH levels, < 240 IU/l survival is significantly better.

Adult↗
PubMed1998

Expression of adhesion molecules on granulocytes and monocytes from patients with asthma stimulated in vitro with interleukin-8 and monocyte chemotactic protein-1.

Upregulation of adhesion molecule expression on endothelial cells (EC) and circulating leukocytes, by locally produced inflammatory mediators, may result in the enhanced infiltration of leukocytes into tissue, e.g. the airways of asthma patients. The present study investigates whether the expression of adhesion molecules on granulocytes and monocytes from asthma patients is affected by chemotactic factors, i.e. interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1). Flow cytometric analysis showed that the intrinsic expression of the various adhesion molecules on peripheral blood phagocytes from asthma patients was not different from that of healthy individuals. However, stimulation of monocytes with MCP-1 resulted only in upregulation of the expression of CD14 on monocytes from symptomatic asthma patients but not on monocytes from asymptomatic asthma patients and healthy individuals. Stimulation of granulocytes with IL-8 did not change the expression of the various beta 1- and beta 2-integrin molecules, such as VLA-4, LFA-1, CR3 and p150,95. Since earlier studies have shown that CD14 on monocytes mediates monocyte adhesion to activated vascular EC the present findings suggest that during the active phase of asthma upregulation of CD14 on monocytes by MCP-1 may lead to an increased adhesion of monocytes to vascular endothelium and their subsequent transendothelial migration into the tissue of the airways.

Adolescent↗
PubMed1997

The development of the 'Quality-of-life for Respiratory Illness Questionnaire (QOL-RIQ)': a disease-specific quality-of-life questionnaire for patients with mild to moderate chronic non-specific lung disease.

Chronic non-specific lung disease (CNSLD) encompasses asthma as well as chronic obstructive pulmonary disease (COPD). Recently in health care, there has been increasing awareness in the functional, psychological and social aspects of the health of patients; their quality of life (QOL). Quality-of-life research addressing CNSLD patients has been rather underdeveloped for a long period of time. Recently, however, the importance of QOL is being increasingly recognized, and several research groups have started to study QOL in CNSLD patients in more detail. This paper describes the construction of a disease-specific QOL instrument for patients with mild to moderately severe CNSLD. Items relating to several domains of QOL were listed, and 171 CNSLD patients in general practice were asked how much of a problem each item had been (assessed on a seven-point Likert scale). After applying an item-selection procedure, a uni-dimensional QOL questionnaire was constructed consisting of 55 items divided into seven domain subscales: breathing problems, physical problems, emotions, situations triggering or enhancing breathing problems, general activities, daily and domestic activities, and social activities, relationships and sexuality. Reliability estimates of the domain subscales of the constructed questionnaire varied from 0.68 to 0.89, and was 0.92 for the QOL for Respiratory Illness Questionnaire (QOL-RIQ) total scale. A first impression of the construct validity of the questionnaire was gained by investigation of the relationship between the QOL domain subscales and several indicators of illness severity, as well as the relative contribution of illness severity variables, background characteristics and symptoms to QOL, using regression analysis. Further research to validate the questionnaire to a greater extent (construct validity, test-retest reliability and responsiveness to change) is currently taking place.

Adolescent↗
PubMed1997

Association of anxiety with perception of histamine induced bronchoconstriction in patients with asthma.

BACKGROUND: The perception of bronchoconstriction varies among patients with asthma and this perception may be related to the covariation of sensory and affective aspects of dyspnoea. A study was performed to evaluate whether there are differences in the perception of histamine induced bronchoconstriction between anxious and non-anxious perceivers and whether anxious perception of bronchoconstriction can be predicted by higher levels of baseline anxiety. METHODS: Seventy eight asthmatic subjects referred for a histamine challenge test undertook baseline measures for anxiety symptomatology and forced expiratory volume in one second (FEV1) followed by perceived breathlessness (Borg scale), anxiety (SUDS), and FEV1 measurement before and during induced bronchoconstriction. Based on the correlation between Borg and SUDS scores, the patients were divided into anxious and non-anxious perceivers. RESULTS: Forty one patients reported no anxiety during the challenge test. The anxious perceivers (n = 20) had higher levels of perceived breathlessness and anxiety at 20% fall in FEV1 and were more accurate in their perception of airways obstruction than non-anxious perceivers (n = 58). However, they did not report higher baseline levels of anxiety symptomatology. CONCLUSIONS: Anxiety experienced during bronchial challenge testing may result from the accurate perception of physiological changes and further direct attention to airways obstruction.

Adult↗
PubMed1997

Enhanced expression of neutral endopeptidase (NEP) in airway epithelium in biopsies from steroid- versus nonsteroid-treated patients with atopic asthma.

The expression of the endogenous neuropeptide-degrading enzyme, neutral endopeptidase (NEP; CALLA, CD10, E.C.3.4.24.11) on cultured human airway epithelial cells can be upregulated by corticosteroids. We examined whether NEP expression in the airway epithelium or lamina propria in bronchial biopsies is enhanced in atopic asthmatics on regular inhaled steroids as compared with those without steroid treatment. Forty nonsmoking adults (age 19 to 48 yr) with mild to moderate asthma (forced expiratory volume in 1 s > or = 50% pred., histamine PC20 range 0.02 to 7.6 mg/ml) with (n = 23) or without (n = 17) regular inhaled steroids treatment entered the study. Biopsies were taken at (sub)segmental level from the right lower lobe, the middle lobe, and the main carina. Immunohistochemical staining was performed on cryostat sections using the VIL-A1 monoclonal antibody against CD10 (NEP). Intra- and inter-observer repeatability of a semiquantitative scoring method was good as assessed by weighted kappa (kappa(w) ranging from 0.66 to 0.81). In the airway epithelium, NEP-positive sites were within the basal layer and, in contrast with studies applying other antibodies, also at apical sites and within the lamina propria. In both the epithelium and lamina propria, NEP expression was not significantly different between the three biopsy sites (Friedman's nonparametric two-way analysis of variance; P > 0.68), nor was expression in the lamina propria associated with inhaled steroid usage (Mann-Whitney U test; P = 0.98). However, NEP expression was significantly enhanced in the airway epithelium in patients using inhaled steroids as compared with nonsteroid users (mean rank: 23.4 and 15.5, respectively; P = 0.02). Among nonsteroid-using subjects, NEP expression was related to symptoms and the methacholine PC20 (Rs: -0.69 and 0.49, respectively; P < or = 0.04). We conclude that the expression of NEP is enhanced in airway epithelium in bronchial biopsy specimens from patients with atopic asthma who are regularly using inhaled steroids as compared with patients who do not. This fits the hypothesis that the anti-inflammatory effect of corticosteroids within the airways is partially mediated by the upregulation of the endogenous neuropeptide-degrading enzyme NEP.

Adrenergic beta-Agonists↗
PubMed1997

Repeatability of measures of inflammatory cell number in bronchial biopsies in atopic asthma.

Airway pathology is increasingly considered to be a major outcome in asthma research. The aim of this study was to examine the intra-observer, within-section and between-biopsy repeatability, together with the implications for statistical power of a computerized quantitative analysis of inflammatory cell numbers in the lamina propria in bronchial biopsy specimens from atopic asthmatic subjects. Thirty six atopic adults (aged 19-40 yrs) with mild to moderate asthma (baseline forced expiratory volume in one second (FEV1) > or =50% of predicted value, methacholine (PC20) range 0.02-18.2 mg x mL[-1]) at various levels of treatment (25 subjects on inhaled steroids) entered the study. Biopsies were taken from the (sub)segmental carinae of the right lower and middle lobe and from the main carina. Specimens were snap-frozen and immunohistochemical staining was performed on cryostat sections with monoclonal antibodies against: (secreted) eosinophil cationic protein (EG1, EG2), mast cell tryptase (AA1), CD45, CD22, CD4, CD8, CD25, and CD45RO. Using a computerized system, the number of positively stained cells in the lamina propria was counted. When considering all cell types together, satisfactory intraclass correlation coefficients (ICC) values were obtained for intra-observer, within-section and between-biopsy repeatability, being 0.90, 0.80 and 0.81, respectively. The analysis of repeatability for individual cell types revealed ICC values ranging 0.47-0.82 for intra-observer, 0.44-0.76 for within-section and 0.37-0.67 for between-biopsy repeatability. The results imply that a sample-size between eight and 25 subjects is needed to detect at least one doubling difference in cell number per 0.1 mm2 for a particular inflammatory cell type in a study, using a within-group design with alpha=0.05 and power of 0.80. A sample-size of 13-48 subjects per group is required to detect the same difference between the groups in a parallel design.

Adult↗
PubMed1997

Comparison of inflammatory cell counts in asthma: induced sputum vs bronchoalveolar lavage and bronchial biopsies.

BACKGROUND: Induced sputum potentially allows monitoring of airway inflammation in patients with asthma in a non-invasive way. However, the relationship between the cellular content in sputum and airway tissue has not been fully clarified. OBJECTIVE: We compared the cellular compositions of hypertonic saline-induced sputum, bronchoalveolar lavage fluid (BAL) and bronchial biopsies in 18 clinically stable patients with mild to moderate atopic asthma (baseline FEV1: range 61-114%pred, PC20 methacholine: 0.04-4.7 mg/mL). They were treated with inhaled short-acting bronchodilators on demand, with (n = 8) or without (n = 10) regular inhaled steroids. METHODS: Each patient underwent sputum induction and fiberoptic bronchoscopy on separate days in random order. Differential cell counts of induced sputum, bronchoalveolar lavage and bronchial wash were determined on May-Grünwald-Giemsa stained cytospins. Flow cytometry was performed on sputum and BAL samples. Immunohistochemical techniques were used to stain inflammatory cells in 6 microm cryostat sections of bronchial biopsies. RESULTS: Sputum cell differentials were not different between the patients with and without inhaled steroids, and showed a median value of 19.4% squamous cells, with 1.0% eosinophils, 3.3% lymphocytes, 28.7% neutrophils, 49.4% macrophages and 6.9% cylindric epithelial cells (in percentage non-squamous cells). The percentage eosinophils in sputum was significantly correlated with their percentage in bronchial wash (Rs = 0.52, P = 0.03) and in BAL (Rs = 0.55, P= 0.02), whilst there was a trend towards such a correlation between the number of eosinophils/mL sputum and the number of EG2+ eosinophils/mm2 lamina propria in bronchial biopsies (Rs = 0.44, P = 0.07). In addition, the percentage of CD4+ lymphocytes correlated between sputum and BAL (Rs = 0.55, P = 0.03). CONCLUSION: We conclude that the eosinophil counts in hypertonic saline-induced sputum from patients with asthma are related to those in bronchial wash and BAL and, to a lesser extent, with the counts in bronchial biopsies. This suggests that induced sputum can be used to monitor the presence and severity of airway inflammation in asthma.

Adolescent↗
PubMed1996

[Good results of outpatient pulmonary rehabilitation: 2-year experience in the Rijnlands Zeehospitium in Katwijk].

OBJECTIVE: To describe the results of outpatient pulmonary rehabilitation of patients with asthma and chronic obstructive pulmonary disease (COPD). DESIGN: Descriptive. SETTING: Rijnlands Zeehospitium, Katwijk, the Netherlands. METHODS: In the period June 1991-September 1993, 64 patients participated in pulmonary rehabilitation. They were divided into three groups according to the results of spirometry: group I: FEV1 > 60% of predicted value; group 2: FEV1 40-60%; group 3: FEV1 < 40%. Data were collected by spirometry, bicycle ergometry, walking distance and the Questionnaire for asthma and COPD-patients, which measures quality of life, compliance with therapy, ability to cope and social support. Patients visited the outpatient clinic three times a week, during three months for training and guidance in a multidisciplinary setting, and attended a health education programme. RESULTS: Significant results were obtained in exercise performance at bicycle ergometry and walking distance. The psychosocial results showed improvement in quality of life, compliance with therapy and ability to cope. Group 1 and group 2 improved on almost every parameter, in group 3 the results in exercise performance were less striking. With respect to psychosocial parameters, group 3 showed significant reduction in anger, dyspnoea and fatigue. CONCLUSION: Pulmonary rehabilitation on an outpatient basis showed positive results that were most striking in patients with asthma or mild COPD. The results in patients with severe COPD were less, but still evident.

Activities of Daily Living↗
PubMed1996

Hb Malmö [beta-97(FG-4)His-->Gln] leading to polycythemia in a Dutch family.

We have examined six individuals from a two-generation Dutch family for a suspected hemoglobin (Hb) abnormality. The propositus presented with polycythemia and complained of persistent weakness, headache, and epistaxis. All family members initially showed a normal Hb-electrophoretic pattern, but on isoelectric focusing, three of them displayed a fast-moving band associated with high packed red cell volumes (PCV) and increased red blood cell count. The Hb mutant was analyzed at the DNA level by specific gene fragment amplification (PCR), followed by direct DNA sequencing, and the mutation was confirmed by restriction enzyme analysis. We found a C-->G transversion (CAC-->CAG) at codon 97 of the beta-chain, which corresponded to the His-->Gln amino acid substitution previously described as Hb Malmö. We report here the clinical history of the patient, the effects of phlebotomy treatment, and the effect of subnormal iron conditions on the erythropoietic recovery after phlebotomy. The mechanism responsible for the induction of the higher oxygen affinity is discussed, as are some aspects concerning the occurrence, pathology treatment, and the genetic risk of Hb variants with high O2 affinity.

Adult↗
PubMed1996

Is there a specific relationship between asthma and panic disorder?

The objective of the present study was three-fold: (1) to assess the prevalence of PD in asthmatic patients in comparison with non-asthmatic patients; (2) to investigate possible differences in pulmonary function and anxiety symptomatology between asthmatic patients with PD and those without; and (3) to evaluate possible differences in symptom perception during histamine-induced bronchoconstriction between asthmatic patients with PD versus asthmatic controls without PD matched for age, sex and bronchial responsiveness to histamine (PC20). The study was performed on 123 consecutive patients referred to the lung function laboratory of a university hospital for a histamine challenge test. Firstly, baseline measures for FEV1, anxiety (ADIS-R, ACQ, BSQ, and STAI) and depression (SDS) were collected. Subsequently, before and during induced bronchoconstriction FEV1, perceived breathlessness (Borg scale), subjective anxiety (SUDS), and somatic panic symptoms (PAQ) were assessed. The prevalence of PD in asthmatic patients, although higher than in the general population, was very similar to the rate observed in non-asthmatic patients. Baseline level of FEV1 and bronchial responsiveness to histamine (PC20) were also not significantly different between asthmatic patients with and without PD. Moreover, in comparison with matched controls, PD cases reported significantly higher levels of perceived breathlessness during induced bronchoconstriction, although their mean fall in FEV1 was very comparable. It is concluded that the higher prevalence of PD in asthma is non-specific and probably due to selection bias.

Adult↗
PubMed1996

Interstitial lung disease with pleural effusion caused by simvastin.

Simvastin, a HMG-CoA reductase blocker, is used for the treatment of certain forms of hypercholesterolaemia. Simvastin is prescribed to lower high serum levels of cholesterol by inhibiting a specific enzyme, hydroxy-methylglutarylCo-enzym-A (HMG-CoA) reductase. This ultimately leads to an increase of the number of LDL-receptors in the liver, and thus, to a decrease of the serum LDL-cholesterol. To a much lesser extent it lowers the serum VLDL-cholesterol and makes the serum HDL-cholesterol level rise. In general, this relatively new compound is well tolerated and only a few, mostly minor, adverse effects have been reported so far. We present a patient who developed interstitial lung disease with pleural effusion most probably as a result of the use of Simvastin.

Anticholesteremic Agents↗