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Biomedical subjects

G Wesseling

Publications and source records attributed to G Wesseling.

18 recordsLinked to original sources

[Relationship between the composition of fine dust particles in the air and lung function in school children].

OBJECTIVE: To determine whether or not there is a relationship between the lung function of school children and the ability of fine dust particles in the air to generate radicals. DESIGN: Descriptive. METHOD: Six primary schools in locations with different traffic volumes were selected in Maastricht, the Netherlands. Air samples were taken in these schools over a period of 4 days; the concentration of fine dust was measured in the 6 pooled samples. Lung function tests were performed in children in the age of 8-13 and their parents filled out a questionnaire on the state of their children's health. RESULTS: An average of 66% of the children (184 girls and 158 boys, with an average age of 10 years (range: 8-13 years)) participated. The average FEV1 for the children from the 6 schools was not related with the total amount of fine dust particles in the air. However, a lower average FEV1 was associated with a higher radical-generating capacity in the air samples. No direct association was observed between the radical-generating capacity of the dust and the traffic intensity. CONCLUSION: There was a clear relationship between lung function and the radical-generating capacity of fine dust in the air. On the basis of these findings future guidelines could be based on chemical properties of the fine dust particles and not exclusively on the quantity of fine dust.

English Abstract↗

[The treatment of asthma: indications for a change in approach].

In both children and adults with persistent asthma, treatment with an inhaled corticosteroid (ICS) is recommended. Moreover, inhaled bronchodilating agents have a clear role to play. The minimum effective dose of an ICS in the individual patient can be determined either by starting with a low dosage of ICS and increasing the dosage gradually on the basis of the symptoms (the 'step-up' approach), or by starting with a high dosage and, if the results are good, decreasing it to the pointwhere adequate control is maintained (the 'step-down' approach). In a study of the step-up approach with the ICS fluticasone, with or without salmeterol as a long-acting beta2-agonist (LABA) in adult patients with asthma, the approach with salmeterol produced the best results, namely, good asthma control in 71% of the patients and total control in 41%. In a study involving both children and adults with asthma, good results were obtained from treatment with a relatively low maintenance dose of ICS (budesonide) combined with a LABA (formoterol), whereby patients were permitted to use additional inhalations of the combination ICS and LABA. How the different therapeutic concepts result in long-term control, what the side effects are in the long term, and whether, in addition to the clinical symptoms, laboratory findings are also important as a therapeutic criterion are all unknown.

Administration, Inhalation↗

Association between first-degree familial predisposition of asthma and atopy (total IgE) in newborns.

BACKGROUND: It is generally thought that infants with a first-degree familial predisposition of asthma are at higher risk of developing asthma than infants without predisposition. OBJECTIVE: To investigate whether there is an association between being at high risk for developing asthma and increased level of total IgE in newborns and whether total IgE is influenced by gender, family size, birth season, maternal smoking, birth weight, gestational age, and maternal diet. METHODS: Two hundred and twenty-one high risk and 308 low-risk infants were prenatally selected in a 5-year-period. Three to 5 days after birth, the total IgE was measured in capillary heel blood. RESULTS: Data on total IgE and first-degree familial predisposition were available for 170 high-risk and 300 low-risk infants. There was a statistically significant relationship between being at high-risk (maternal asthma) and increased levels of total IgE in newborns (total IgE cut-off levels: 0.6-0.9 IU/mL (odds ratio (OR)=2.1, 95% confidence interval (CI): 1.2-3.7 to 3.0, 95% CI: 1.5-5.9)), between being born in autumn and increased levels of total IgE in newborns [total IgE cut-off levels: 0.5-0.6 IU/mL (OR=2.5, 95% CI: 1.2-5.1 to 2.5, 95% CI: 1.2-5.4)] and between maternal vitamin supplements intake and decreased levels of total IgE in newborns (total IgE cut-off level: 0.9 IU/mL (OR=0.5, 95% CI:0.3-1.0)). There was no interaction between the effects of maternal asthma and birth season on total IgE, as well as between the effects of maternal asthma and maternal vitamin supplements intake. Gender, family size, maternal smoking, birth weight, and gestational age did not influence the associations. CONCLUSION; Being at high-risk of asthma (maternal asthma) and birth season are positively associated with the presence of increased levels of total IgE at birth, whereas maternal vitamin supplements intake is negatively associated with the presence of total IgE at birth.

Adult↗

Chronic bronchiolitis in a 5-yr-old child after exposure to sulphur mustard gas.

Exposure to sulphur mustard (SM) gas may have extensive immediate effects on the respiratory system. However, long-term effects are far less known. This case report describes a Kurdish male child who was exposed to SM gas during a chemical attack in Iraq at 5 yrs of age. In the acute phase, the child developed severe respiratory symptoms with a chemical pneumonia. Extensive burning of the skin occurred. In the course of 10 yrs, lung function deteriorated progressively to a forced expiratory volume in one second of 30% of predicted value. Severe air-trapping occurred. The lung function abnormalities were not reversed by treatment with corticosteroids or bronchodilators. Infectious exacerbations of the child's lung disease occurred. High resolution computed tomography scan showed multiple bronchiectasis. The histological picture of an open lung biopsy was best described as a "chronic bronchiolitis".

Biopsy↗

Dose dependent increased mortality risk in COPD patients treated with oral glucocorticoids.

Systemic corticosteroids are often administered in COPD patients. The relationship between systemic glucocorticoids and mortality in patients with moderate to severe chronic obstructive pulmonary disease (COPD) was retrospectively analysed. Baseline characteristics of the patients, in stable clinical condition, were collected on admission to a pulmonary rehabilitation centre. Overall mortality was asessed at the end of follow-up. The Cox proportional hazards model was used to quantify the relationship between glucocorticoid use, distinguishing administration route (oral/inhalation) and oral dose, and overall mortality, adjusted for the influence of age, sex, smoking, lung function, resting arterial blood gases and body mass index. On multivariate analysis, oral glucocorticoid use at a (prednisone equivalent) dose of 10 mg x day(-1) without inhaled glucocorticoids, was associated with an increased risk (RR=2.34, 95% confidence interval (CI) 1.24-4.44) while 15 mg x day(-1) carried a relative risk of 4.03, CI = 1.99-8.15). A significant interaction was observed between inhaled and oral glucocorticoid use. Combined with inhaled glucocorticoids, the relative risk of oral glucocorticoid use appeared to be significantly smaller. It is concluded that in severe chronic obstructive pulmonary disease, maintenance treatment with oral glucocorticoids is associated with increased mortality in a dose-dependent manner. Since the present study design cannot exclude the possibility of bias by indication, further prospective studies are indicated using a broader patient characterization.

Administration, Oral↗

Interaction between glucocorticoids and beta2-agonists: alpha and beta glucocorticoid-receptor mRNA expression in human bronchial epithelial cells.

Recent studies have suggested that regular use of beta2-agonists has adverse effects on asthma control, due to the cross-talk between cAMP responsive element binding proteins (CREB) and glucocorticoid receptors (GR). The aim of this study was to investigate the interaction between GR and CREB on cytoplasmic protein level with a gel mobility shift assay and to determine the effect of this interaction on mRNA levels by Northern blot analysis. After exposing human bronchial epithelial cells for 1 hr to either 1 microM terbutaline or budesonide, more binding of CREB and GR, respectively, was observed to their responsive elements in DNA. Simultaneous exposure to terbutaline and budesonide also increased the binding of CREB and GR to DNA. After 4 hr, both alpha and beta GR mRNAs were down-regulated by 1 microM budesonide. Simultaneous addition of 1 microM terbutaline prevented this down-regulation. Adding 100 times more budesonide compared to terbutaline again down-regulated both GR forms, although significantly less compared to the down-regulation induced by 1 microM budesonide alone. Addition of terbutaline to cells already exposed to budesonide did not reverse the GR mRNA expression within 44 hr. Similar results were obtained with metallothionein-2 (MT2) mRNA levels. In conclusion, beta2-agonists interfere with the GR function in human bronchial epithelial cells when given simultaneously, with this being overcome by sequential exposure of the cells to first glucocorticoids and later beta2-agonists.

Activating Transcription Factor 2↗

Acute effects of nebulized salbutamol on resting energy expenditure in patients with chronic obstructive pulmonary disease and in healthy subjects.

This study investigated the contribution of a single dose of salbutamol by nebulizer to the increased resting energy expenditure (REE) frequently found in patients with chronic obstructive pulmonary disease (COPD) (n = 22), in comparison with a younger (n = 15) and an older healthy (n = 10) control group. The rise in REE after nebulization of 5 mg salbutamol was significantly higher in younger (11.4%) compared to older healthy subjects (5.7%; p < 0.05) and patients with COPD (4.2%; p < 0.001), which also accounted for the increase in heart rate and the drop in the respiratory quotient. No differences in metabolic effects were found between older control subjects and patients with COPD. In conclusion, despite significant improvements in FEV1 and airway resistance, a significant rise in REE was observed in patients with COPD after nebulization of salbutamol. The metabolic effects of salbutamol were however not sufficient to explain totally the elevated REE seen in these patients.

Adult↗

In vitro and in vivo modulation of alpha- and beta-glucocorticoid-receptor mRNA in human bronchial epithelium.

Despite the central role bronchial epithelial cells play in asthmatic reactions, and the widespread use of inhaled corticosteroids in asthma, no information is available on the effect of glucocorticoids on glucocorticoid- receptor (GR) gene expression. In this study, the effect of budesonide on alpha- and beta-GR gene expression in human bronchial epithelial cells was investigated in vitro and in vivo. A bronchial epithelial cell line was exposed in vitro to budesonide, and a dose- and time-dependent synchronous downregulation of alpha- and beta-GR mRNA was observed. A 1-h exposure resulted in a reversible and reduced downregulation as compared with continuous exposure. In healthy volunteers (n = 10), no difference on average was present in GR mRNA expression before or after 4 wk of budesonide inhalation in either bronchial epithelial cells or alveolar macrophages. The time between the last inhalation and sampling of cells ranged from 0.5 to 8 h. However, a significant downregulation of alpha-GR mRNA was observed when the time between the last inhalation and sampling of cells was more than 2 h. Normalization of the downregulation of GR mRNA expression in bronchial epithelial cells is explained by the pharmacokinetics of inhaled budesonide in the human lung.

Administration, Topical↗

Adverse effects of the indoor environment on respiratory health in primary school children.

Exposure to various factors from the indoor environment on respiratory health of 470 Dutch primary school children was studied. We investigated which of the factors, such as home dampness, passive smoking, unvented kitchen geysers, or pets, affected children's respiratory health the most, and whether airway sensitivity to these indoors exposures differed between boys and girls. Information on respiratory morbidity and characteristics of the housing was obtained by a written questionnaire, completed by the parents of the children. Lung function of the children was measured at school, by forced oscillation technique (FOT) and spirometry. In boys, all investigated lung function parameters were significantly affected by exposure to passive smoking during the child's entire life. Although mostly nonsignificant, all of the reported asthma-like symptoms were related especially to maternal smoking, with a trend of a dose-response relationship. Furthermore, damp stains (P < 0.05) and mold growth (ns) were associated with chronic cough and with small but significant impairments in part of the lung function parameters. No consistent patterns were observed with unvented kitchen geysers and pets. Although passive smoking (cumulative dose) in girls was also associated with lung function impairments, the effects were smaller than those in boys and not all significant. Associations between the asthma-like symptoms and the dose of maternal and paternal smoking also were less consistent. Furthermore, no associations were found with the dampness indicators and with pets, but unvented kitchen geysers were significantly related to impairments in some of the impedance indices. This study shows detrimental effects of several indoor factors on the prevalence of chronic respiratory symptoms and lung function in children, which are most pronounced for passive smoking, and somewhat less pronounced for dampness and the presence of unvented kitchen geysers. Airway sensitivity to these exposures appeared to be higher in boys than in girls.

Air Pollution, Indoor↗

Acute respiratory effects of low level summer smog in primary school children.

We aimed to study the possible effects of exposure to a summer smog episode on the respiratory health of 212 school children. Furthermore, the suitability of the forced oscillation technique (FOT) to demonstrate such effects was evaluated. Acute respiratory symptoms were evaluated by questionnaire and lung function was assessed by spirometry and respiratory impedance measurements. For each child, comparisons were made between measurements performed at baseline (low levels of air pollutant: 55 micrograms.m-3 for SO2 and 58 micrograms.m-3 for NO2 (maximum 24 h means); O3 levels ranged from 2-56 micrograms.m-3 (8 h mean)); and after a summer smog episode (characterized by 8 h O3 levels > 120 micrograms.m-3 (163 micrograms.m-3) and 1 h levels > 160 micrograms.m-3 (215 micrograms.m-3). No significant effects were observed on the prevalence of acute respiratory symptoms. When individual changes in lung function indices (delta LF) were regressed on changes in previous day ozone (8 h mean) and changes in mean daily temperature (delta MTemp), using multiple linear regression analysis, a significant negative association was observed with peak expiratory flow (PEF), but not with other spirometry indices. Although significant associations were observed with reactance at 8 Hz (Xrs8), resonant frequency (f0) and frequency dependence of resistance (FD), the signs of the beta s were opposite to the direction expected when O3 adversely affected the impedance outcomes. In conclusion, in this study short-term exposure to moderately high levels of ozone did not result in clear adverse effects on the respiratory health of the children.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Acute respiratory effects of summer smog in primary school children.

In 535 primary school children we studied the effects of exposure to summer smog on respiratory health. Baseline measurements were performed during low air pollution levels (max. 24-h concentrations of SO2, O3 and NO2 were 55, 49 and 58 micrograms/m3, respectively) consisting of lung function measurements using spirometry and the forced oscillation technique (FOT) and the prevalence of respiratory symptoms, determined by a written questionnaire. During a summer smog episode, 212 randomly chosen children were re-examined, characterised by 8-h ozone levels > 120 micrograms/m3 (max. 163 micrograms/m3) and 1-h ozone levels > 160 micrograms/m3 (max. 215 micrograms/m3). Overall, small decrements were observed in the forced expiratory volume in 1 s (FEV1), (P < 0.05) and the forced expiratory volume between 25 and 75% of the vital capacity (FEF25-75%) (P < 0.01). On the contrary, there was a statistically significant decrease in resistance parameters. No increases were observed in the prevalence of acute respiratory symptoms. In conclusion, in this study we found small inconsistent changes in lung function and no increase of respiratory symptoms after short-time exposure to moderately high ozone levels.

Acute Disease↗

Frequency dependence of oscillatory resistance in healthy primary school children.

With the use of the forced oscillation technique, respiratory input impedance was measured in 371 healthy children, aged 5-12 years. How impedance values varied with height (age) and gender and to what extent negative frequency dependence of oscillatory resistance existed in these children was investigated. Negative frequency dependence of resistance between 8 and 28 Hz was a common finding in all height categories. With increasing height, resistance decreased and reactance increased in all children. Below 140 cm of height, resistance values at 8 Hz were higher, and reactance values at 8 Hz were more negative in girls than in boys. At heights above 140 cm the reverse was found. Resonant frequency was found to be higher in boys than in girls. The incidence of negative frequency dependence of resistance (FD) decreases during growth. Over heights of 130-160 cm, more negative FD existed in boys than in girls. It can be concluded that negative FD between 8 and 28 Hz can be found in healthy children up to 12 years of age, most pronounced in boys, not necessarily implicating pulmonary pathology.

Airway Resistance↗

Gastric asthma? No change in respiratory impedance during intraesophageal acidification in adult asthmatics.

BACKGROUND: In patients with asthma, gastroesophageal reflux (GER) has been shown to be a common finding, and a number of investigators have suggested that reflux may have a deleterious effect in asthma, either as a result of recurrent (micro)aspiration or by some form of a reflex mechanism. AIM OF THE STUDY: To measure changes in lung function in response to intraesophageal acid perfusion in asthmatics with GER. METHODS: In 12 patients with bronchial asthma and complaints suggesting GER with increased reflux scores during 24-h intraesophageal pH monitoring, impedance measurements of the respiratory system using the technique of forced oscillations and spirometry were performed after intraesophageal acidification. RESULTS: No statistically significant changes in FEV1 or in respiratory impedance were demonstrated after intraesophageal acid provocation. CONCLUSION: No direct effect of intraesophageal acidification on bronchomotor tone was demonstrated in asthmatics with GER.

Administration, Inhalation↗

A comparison of the effects of anticholinergic and beta 2-agonist and combination therapy on respiratory impedance in COPD.

The effects of three different regimens of inhaled bronchodilators on spirometry and respiratory impedance as measured with the technique of forced oscillations were compared in a double-blind crossover study in 22 patients with stable chronic obstructive pulmonary disease (FEV1 less than 70 percent predicted). On three trial days, patients inhaled, in random order, 40 micrograms ipratropium bromide, 200 micrograms fenoterol hydrobromide, or a combination of 40 micrograms ipratropium and 100 micrograms fenoterol from a powder inhaler, followed by a second dose of the same drug after 60 min. The effects were measured at baseline and 20, 40, 60, and 120 min after the first inhalation. No significant decrease in total respiratory resistance at 8 Hz (Rrs [8]) was observed after ipratropium, whereas Rrs (8) decreased significantly 20 min after fenoterol and 40 min after the combination regimen (p less than 0.05). All three studied drugs resulted in a significant increase in the reactance (p less than 0.01) and decrease in resonant frequency. Both fenoterol (delta FEV1 34 percent, p less than 0.0001) and the combination regimen (delta FEV1 38 percent, p less than 0.0001) resulted in a significantly larger increase in FEV1 than ipratropium alone (delta FEV1 17 percent, p less than 0.0001). A second dose of fenoterol and of the combination regimen resulted in a further significant increase in FEV1 after 120 min (p less than 0.05). A second dose of ipratropium did not result in a further significant increase in FEV1. The changes in respiratory impedance were qualitatively similar for all three drug regimens, but larger in absolute terms after fenoterol and the combination regimen than after ipratropium. The similar effect of these drugs on the reactance can be explained by an increase in the capacitance of the respiratory system, and in combination with a decrease in frequency dependence of resistance, by assuming a decrease in peripheral airway resistance.

Aged↗

Oscillatory mechanics of the respiratory system in neuromuscular disease.

Respiratory impedance measurements by means of the technique of forced oscillations together with spirometry and measurements of maximal mouth pressures were performed in 27 patients with a variety of neuromuscular disorders to assess the value of adding respiratory impedance measurements in the evaluation of lung function in neuromuscular disease. Using the technique of forced oscillations, impedance measurements are easily performed in physically disabled persons, since they require little active cooperation and no forced respiratory maneuvers. Normal respiratory impedance characteristics were found, although resistance values were somewhat higher than those found in normal subjects, signifying the absence of airflow limitation. Spirometric values were markedly reduced, as were maximal mouth pressures. No significant correlations were found between the forced expiratory volumes in 1 s (FEV1) and the impedance data. A strong curvilinear relationship was observed between Pemax and the RV/TLC ratio and a strong correlation existed between FEV1 and Premax. It is concluded from our study that forced oscillometry is a useful tool for the assessment or exclusion of airflow obstruction in patients with neuromuscular disorders when plethysmography is difficult to perform and forced expiratory flow-volume data reflect muscle weakness rather than airflow limitation.

Adolescent↗

Effects of inhalation of beta 2-sympathicomimetic and anticholinergic agents on the impedance of the respiratory system in normal subjects.

Impedance measurement of the respiratory system by forced oscillations is a sensitive and accurate method to detect mechanical parameters, especially in normal subjects. The effects of inhalation of 0.2 mg of fenoterol and 0.02 mg of ipratropium bromide on the impedance of the respiratory system was studied in 20 healthy subjects in a frequency spectrum between 4 and 52 Hz. Both agents caused a statistically significant decrease in resistance (Rrs). Inhalation of fenoterol and ipratropium bromide caused a significant increase in reactance (Xrs). The decrease in Rrs was greater after inhalation of fenoterol than after ipratropium bromide. Fenoterol and ipratropium bromide caused qualitatively similar changes in Rrs and Xrs of the respiratory system. The changes in Rrs can be explained by dilation of the central airways. The changes in Xrs are supposed to be the result of an increase in the capacitance of the lungs.

Administration, Inhalation↗