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Biomedical subjects

W M van Aalderen

Publications and source records attributed to W M van Aalderen.

At least 19 recordsLinked to original sources

[Guideline 'Treating asthma in children' for pediatric pulmonologists (2nd revised edition). I. Diagnosis and prevention].

The case history and physical examination form the corner-stones for asthma diagnosis. Establishing the correct diagnosis may be difficult in infants and preschool children; in such cases the progression of the symptoms over time is important. Routine laboratory and radiological investigations are advised against. Allergy testing may be useful in children under the age of 4 years. Lung function investigations can be used from the age of 5 to 6 years onwards. Non-invasive investigations into the degree of bronchial inflammation can be performed by measuring the fraction nitric oxide in exhaled air. House dust mite reduction is a useful measure for preventing asthma if sensitisation has been demonstrated. Breast-feeding during the first 4 to 6 months of life can be considered as a preventive measure in infants with an increased risk of developing asthma and allergy.

Age Factors↗

Local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity.

To investigate the role of cell-mediated immunity during respiratory syncytial virus (RSV) infection, interferon (IFN)-gamma and interleukin (IL)-10 levels in nasopharyngeal secretions were measured in infants with lower respiratory tract infection (LRTI) caused by RSV. A novel technique was used to measure in vivo cytokine levels in nasopharyngeal aspirates (NPAs). Cytokine levels in the NPAs of 17 mechanically ventilated infants and 43 nonventilated hospitalized infants were compared. As expected, mechanically ventilated infants were significantly younger than nonventilated infants (7 vs. 14 weeks). IFN-gamma levels were above the limit of detection in the NPAs of 3 (18%) mechanically ventilated infants and in the NPAs of 26 (60%) nonventilated infants. IL-10 levels in the NPAs of mechanically ventilated and nonventilated infants were comparable. It is hypothesized that maturation-related mechanisms have a key role in the development of RSV LRTI that results in mechanical ventilation.

Age Factors↗

[Two children with extrapulmonary symptoms due to tuberculosis].

Two patients came to their general practitioner for relatively minor problems: a 4-year-old boy came with a red eye and a 10-year-old girl with red foot soles. They came from Pakistan and Vietnam respectively. Their symptoms were due to tuberculosis, which diagnosis was established by Mantoux test and culture of a stomach aspirate. They were treated accordingly with isoniazid, rifampicin and pyrazinamide and with isoniazid, rifampicin and ethambutol respectively. These cases stress the importance of knowledge of the extrapulmonary manifestations of tuberculosis. As treatment exists and adequate treatment can diminish the reservoir of tuberculosis bacteria, early diagnosis can prevent the morbidity, spread and mortality of tuberculosis.

Antitubercular Agents↗

Inspiratory muscle training in patients with cystic fibrosis.

Little information is available about the effects of inspiratory muscle training in patients with cystic fibrosis (CF). In this study the effects of inspiratory-threshold loading in patients with CF on strength and endurance of the inspiratory muscles, pulmonary function, exercise capacity, dyspnoea and fatigue were evaluated. Sixteen patients were assigned to one of two groups using the minimization method: eight patients in the training group and eight patients in the control group. The training was performed using an inspiratory-threshold loading device. Patients were instructed to use the threshold trainer 20 min a day, 5 days a week for 6 weeks. Patients in the training group trained at inspiratory threshold loads up to 40% of maximal static inspiratory pressure (Pimax) and patients in the control group got 'sham' training at a load of 10% of Pimax. No significant differences were found among the two groups in gender, age, weight, height, pulmonary function, exercise capacity, inspiratory-muscle strength and inspiratory-muscle endurance before starting the training programme. Mean (SD) age in the control group was 19 (5.5) years, mean (SD) age in the training group was 17 (5.2) years. Mean FEV1 in both groups was 70% predicted, mean inspiratory-muscle strength in both groups was above 100% predicted. All patients except one, assigned to the training group, completed the programme. After 6 weeks of training, mean inspiratory-muscle endurance (% Pimax) in the control group increased from 50% to 54% (P = 0.197); in the training group mean inspiratory muscle endurance (% Pimax) increased from 49% to 66% (P = 0.003). Statistical analysis showed that the change in inspiratory-muscle endurance (% Pimax) in the training group was significantly higher than in the control group (P = 0.012). After training, in the training group there was a tendency of improvement in Pimax with an increase from 105 to 123% predicted, which just fell short of statistical significance (P = 0.064). After training no significant differences were found in changes from baseline in pulmonary function, exercise capacity, dyspnoea and fatigue. It is concluded that low-intensity inspiratory-threshold loading at 40% of Pimax was sufficient to elicit an increased inspiratory-muscle endurance in patients with CF.

Adolescent↗

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↗

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↗

Long-term effects of prednisolone in the acute phase of bronchiolitis caused by respiratory syncytial virus.

Follow-up studies have demonstrated that bronchiolitis caused by respiratory syncytial virus (RSV) is strongly associated with wheezing in the ensuing years. During the acute infection the immune response may induce long-lasting detrimental effects, thereby contributing to post-bronchiolitis wheezing (PBW). Therefore, immune-modulating drugs like corticosteroids, administered in the acute phase of RSV bronchiolitis, may prevent PBW and asthma. To evaluate this, we performed a controlled prospective follow-up study after a randomized double-blind placebo-controlled intervention in the acute phase with oral prednisolone. Fifty-four patients under 2 years of age and hospitalized for RSV bronchiolitis between 1992 and 1995 were randomly assigned to prednisolone 1 mg/kg/day for 7 days or placebo. At the mean age of 5 years, 47 patients had completed their follow-up. Patients were divided into four groups: no wheezing, transient wheezing (wheezing during the first year of life); persistent wheezing (wheezing during the first year of life and asthma at the age of 5); and late-onset wheezing (no wheezing during the first year of life but asthma at the age of 5). Prevalence of wheezing and asthma were investigated through an interview by telephone, using a standardized questionnaire. We found no significant differences between the prednisolone- and the placebo-treated group in the number of patients with transient wheezing (8% vs. 17%), persistent wheezing (42% vs. 31%), or late-onset wheezing (17% vs. 13%). We conclude that oral prednisolone during the acute phase of RSV bronchiolitis is not effective in preventing PBW or asthma at the mean age of 5 years. Pediatr Pulmonol. 2000; 30: 92-96.

Acute Disease↗

Respiratory muscle activity measured with a noninvasive EMG technique: technical aspects and reproducibility.

A new method is being developed to investigate airway obstruction in young children by means of noninvasive electromyography (EMG) of diaphragmatic and intercostal muscles. The purpose of this study was to evaluate the reproducibility of the EMG measurements. Eleven adults, 39 school children (20 healthy, 19 asthmatic), and 16 preschool children were studied during tidal breathing on separate occasions: two for adults with a time interval of 3 wk and three for children with time intervals of 1 and 24 h. Single electrodes were placed on the second intercostal space left and right of the sternum and at the height of the frontal and the dorsal diaphragm. Bipolar electrode pairs were placed on the rectus abdominis muscle. A newly designed digital physiological amplifier without any analog filtering was used to measure the EMG signals. Except for the average dorsal diaphragm EMG derivation in healthy school children on the second occasion, a significant correlation between the mean peak-to-peak inspiratory activity of average diaphragmatic and intercostal EMG was found in the different age groups on the different measurement occasions (P < 0.05). To assess the repeatability, we described the agreement between the repeated measurements within the same subjects. No significant differences were found between the measurements on the separate occasions. Our observations indicate that the EMG signals derived from the diaphragm and intercostal muscles are, in different age groups with and without asthma, reproducible during tidal breathing.

Adolescent↗

Monocyte IL-10 production during respiratory syncytial virus bronchiolitis is associated with recurrent wheezing in a one-year follow-up study.

Respiratory syncytial virus (RSV) bronchiolitis is associated with subsequent recurrent wheezing episodes. To determine whether cytokine responses during infection can be of predictive value for the development of recurrent wheezing, we performed a follow-up study in 50 hospitalized children with RSV bronchiolitis. Monocyte and lymphocyte cytokine responses in vitro were studied during the acute phase of disease, and again during the convalescent phase, 3 to 4 wk later. Monocyte cytokine responses, including interleukin-10 (IL-10), were measured in whole blood cultures, stimulated with lipopolysaccharide and interferon-gamma (LPS + IFN-gamma). In addition, T-cell cytokine responses, including IFN-gamma and IL-4 production, were measured in whole-blood cultures stimulated with phytohemagglutinin (PHA) or alphaCD2 + alphaCD28. Cytokine responses were analyzed in relation to the development of recurrent episodes of wheezing, documented by parents in a diary during a 1-yr follow-up period. IL-10 responses during the acute phase of RSV bronchiolitis were comparable to those in healthy control subjects. During the convalescent phase, IL-10 responses were significantly increased in patients as compared with those in healthy control subjects (p < 0.001). At follow-up, 27 children (58%) had recurrent episodes of wheezing. IL-10 levels, measured during the convalescent phase, were significantly higher in patients who developed recurrent wheezing during the year after RSV bronchiolitis than in patients without recurrent episodes of wheezing (p = 0.006). Moreover, IL-10 responses during the convalescent phase correlated significantly with the number of wheezing episodes (r = 0.42, n = 46, p = 0.004). Interestingly, no association was found between IFN-gamma responses, IL-4 responses, or IFNgamma/IL-4 ratios and recurrent wheezing. We conclude that monocyte IL-10 responses in vitro upon stimulation with nonspecific stimuli may have predictive value for the development of recurrent wheezing after RSV bronchiolitis. Moreover, our results indicate that not only allergen-driven Th2 cytokine responses can lead to asthmatic symptoms but also virus-induced changes in cytokine responses may result in asthmatic symptoms.

Bronchiolitis, Viral↗

Clinical effects of air cleaners in homes of asthmatic children sensitized to pet allergens.

BACKGROUND: Exposure to cat and dog allergens is very common in the Western World and is a serious cause of asthma in sensitized subjects. OBJECTIVE: We sought to study the clinical effects of air cleaners in living rooms and bedrooms of asthmatic children sensitized to cat or dog allergens. METHODS: Twenty asthmatic children sensitized to pet allergens (cat/dog) and with an animal at home participated in a double-blind, placebo-controlled, cross-over study in which the effects of air cleaners placed in the living room and bedroom for 3 months were compared with the effects of sham air cleaners. Before and after each study period, lung function, airway hyperresponsiveness (adenosine monophosphate), and peak flow variation were recorded. Cat and dog allergen levels were assessed in the filters of the air cleaners. RESULTS: After a 3-month intervention with active air cleaners, airway hyperresponsiveness decreased significantly, showing a 1.2 doubling dose increase of PC(20 )adenosine (P =.003). Peak flow amplitude also decreased (P =. 045). Substantial amounts of airborne cat and dog allergen were captured by the air cleaners in living rooms and bedrooms as well. Allergen levels in floor dust were not changed. CONCLUSION: In young asthmatic patients sensitized and exposed to pets in the home, application of air cleaners in living rooms and bedrooms was accompanied by a significant improvement in airway hyperresponsiveness and a decrease in peak flow amplitude.

Administration, Inhalation↗

Agreement between spirometry and tracheal auscultation in assessing bronchial responsiveness in asthmatic children.

We have recently found that changes in lung sounds correspond well with a 20% fall in the forced expiratory volume in 1 s (FEV1) after methacholine challenge in asthmatic children. Up to now, little was known about the agreement between a 20% fall in FEV1 and a change in lung sounds after repeated bronchial challenge. In this study we investigated the agreement between the total cumulative histamine dose causing a fall in FEV1 of 20% or more (PD20) and the detection of a change in lung sounds (PDlung sounds) after two bronchial challenges on different occasions in asthmatic children. Fifteen asthmatic children (nine boys), mean age 10.8 years (range 9-15), were studied. All performed two histamine challenge tests on 2 days, with a 24 h to 1 week interval. Lung sounds were recorded over the trachea for 1 min and stored on tape. Lung sounds were analysed directly and also scored from the tape-recording by a blinded second investigator. Wheeze, cough, and an increase in respiratory rate were assessed. The relationship between PD20 and PDlung sounds was calculated by Bland and Altman's measurement of agreement. Eleven children had a positive challenge test (PD20 < or = 16.0 mg ml-1) on both test days; four had a positive challenge on one test day. In 24 out of 26 positive challenges, wheeze, cough, prolonged expiration and/or increased respiratory rate were detected one dose-step before, or at the dose-step of histamine that induced a fall in FEV1 of 20% or more. In two challenges, PD20 was not detected by a change in lung sounds. In four out of four negative challenges (PD20 > 16.0 mg ml-1) no change in lung sounds could be detected. Good agreement between the logarithm of PD20 and the logarithm of PDlung sounds was found on both test days. The mean difference was 0.04 and the limits of agreement (d +/- 2 SD of the differences) were 0.04 +/- 0.41. A good agreement was found between the total cumulative histamine dose causing a fall in FEV1 of 20% or more and the detection of a change in lung sounds after two bronchial challenges on different occasions in asthmatic children.

Adolescent↗

Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis.

The role of cellular immunity in disease severity in respiratory syncytial virus (RSV) bronchiolitis is largely unknown. This study investigated the association between disease severity and systemic cytokine responses in hospitalized ventilated and nonventilated RSV bronchiolitis patients. In whole blood cultures stimulated with phytohaemagglutinin (PHA), lymphoproliferative responses and interferon (IFN)-gamma and interleukin (IL)-4 production during acute illness were measured. In addition, plasma cytokines were measured. Measurements were repeated in the convalescent phase, 3-4 weeks after admission. Fifty patients were included. The median age in ventilaled patients was significantly lower than in nonventilated patients (1 versus 4 months, p<0.05). In comparison with nonventilated patients, the ventilated patients had significantly lower lymphoproliferative responses and a lower production of IFN-gamma and IL-4. In fact, IFN-gamma and IL-4 production in ventilated patients was almost completely undetectable. Plasma IL-8 levels in ventilated patients were significantly higher than in nonventilated patients. In the convalescent phase, lymphoproliferative and cytokine responses as well as plasma IL-8 levels were normal in both patient groups. Since RSV bronchiolitis is associated with the subsequent development of asthma, the possible skewing of the T-helper (Th1/Th2) cytokine balance was investigated. This was found neither in the acute nor in the convalescent phase. In conclusion, the data indicate that depressed lymphocyte function and elevated plasma interleukin-8 levels are markers of severe disease. It is suggested that age and maturation related immune mechanisms could explain the occurrence of severe respiratory syncytial virus bronchiolitis requiring mechanical ventilation in young infants.

Antibodies, Viral↗

Fat malabsorption in cystic fibrosis patients receiving enzyme replacement therapy is due to impaired intestinal uptake of long-chain fatty acids.

BACKGROUND: Pancreatic enzyme replacement therapy frequently fails to correct intestinal fat malabsorption completely in cystic fibrosis (CF) patients. The reason for this failure is unknown. OBJECTIVE: We investigated whether fat malabsorption in CF patients treated with pancreatic enzymes is caused by insufficient lipolysis of triacylglycerols or by defective intestinal uptake of long-chain fatty acids. DESIGN: Lipolysis was determined on the basis of breath 13CO2 recovery in 10 CF patients receiving pancreatic enzyme replacement therapy after they ingested 1.3-distearoyl,2[1-13C]octanoyl glycerol ([13C]MTG). Intestinal uptake of long-chain fatty acids was determined by analyzing plasma [13C]linoleic acid ([13C]LA) concentrations after patients ingested [13C]LA. For 3 d, dietary intakes were recorded and feces were collected. RESULTS: Fecal fat excretion ranged from 5.1 to 27.8 g/d (mean+/-SD: 11.1+/-7.0 g/d) and fat absorption ranged from 79% to 93% (89+/-5%). There was no relation between breath 13CO2 recovery and dietary fat absorption (r = 0.04) after ingestion of [13C]MTG. In contrast, there was a strong relation between 8-h plasma [13C]LA concentrations and dietary fat absorption (r = 0.88, P < 0.001). CONCLUSION: Our results suggest that continuing fat malabsorption in CF patients receiving enzyme replacement therapy is not likely due to insufficient lipolytic enzyme activity, but rather to incomplete intraluminal solubilization of long-chain fatty acids, reduced mucosal uptake of long-chain fatty acids, or both.

Adolescent↗