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Biomedical subjects

J C de Jongste

Publications and source records attributed to J C de Jongste.

At least 19 recordsLinked to original sources
PubMed2001

['Inflammometry' with nitric oxide in exhaled air: a new test for lung diseases].

The gas nitric oxide (NO) is produced in increased amounts in certain types of inflammatory responses and its presence in exhaled air can be demonstrated. The nitric oxide fraction in exhaled air (FeNO) is elevated in patients with asthma and lowered in the case of several other lung diseases such as cystic fibrosis and primary ciliary dyskinesia. The FeNO can be quickly measured in a non-invasive and reproducible manner: on-line if the patient (adult or child), having taken a deep breath in, breathes out with a low flow rate into the NO measuring device or off-line if the expired air is collected in an NO inert reservoir. Confounding factors are contamination of inhaled air with ambient NO and contamination of exhaled air with NO that has been produced in the paranasal sinuses and the nose. The possible applications of FeNO measurement as a new lung function test include diagnostic tests for chronic respiratory symptoms and the possible guidance of anti-inflammatory therapy for asthma and, perhaps, other respiratory disorders.

Breath Tests↗
PubMed2001

Randomised controlled study of clinical efficacy of spacer therapy in asthma with regard to electrostatic charge.

BACKGROUND: Inhalation therapy using a pressured metered dose inhaler (pMDI) and a spacer is frequently used in the treatment of airway disease in children. Several laboratory studies found a clear negative influence of electrostatic charge (ESC) on plastic spacers on the delivery of aerosol. AIMS: To investigate whether ESC on plastic spacers could diminish bronchodilating responses to salbutamol. METHODS: Ninety asthmatic children (aged 4-8 years) were randomised into three groups: metal Nebuchamber, plastic Volumatic, and plastic Aerochamber. The bronchodilating response was measured by the change in peak expiratory flow rate (PEF) after 100 microgram and 400 microgram salbutamol. Within the Volumatic and Aerochamber groups, a crossover comparison was made between electrostatic and non-electrostatic spacers. RESULTS: We found no significant effect of ESC on the bronchodilating response to salbutamol with any of the doses in the Aerochamber and Volumatic groups. For the plastic spacers, the mean difference of the change in PEF after 100 microgram salbutamol between non-electrostatic and electrostatic spacers was only +1.7% (95% CI -1.3% to 4.7%). After 400 microgram salbutamol this was +1.9% (95% CI -1.4% to 5.1%). A comparable efficacy was found for the Nebuchamber, the Aerochamber, and Volumatic with respect to the change in PEF after 100 and 400 microgram salbutamol. CONCLUSION: This study showed no negative influence of ESC on plastic spacers with regard to clinical efficacy of a beta(2) agonist (salbutamol) in children with asthma. The metal Nebuchamber, plastic Aerochamber, and plastic Volumatic were equally effective.

Administration, Inhalation↗
PubMed2001

Controlled low flow off line sampling of exhaled nitric oxide in children.

BACKGROUND: The aim of this study was to validate exhaled nitric oxide (eNO) values obtained with an alternative off line, single breath, low flow balloon sampling method against on line sampling according to ERS and ATS guidelines in children who could perform both methods. METHODS: One hundred and twenty seven white children of median age 14.1 years, all pupils of a secondary school, participated in the study. They performed the two different sampling techniques at three different flows of 50, 100, 150 ml/s. Additional measurements were done in random subgroups to determine the influence of the dead space air on eNO values obtained off line by excluding the first 220 ml of exhaled air. All children completed a questionnaire on respiratory and allergic disorders and underwent spirometric tests. RESULTS: The off line eNO values were significantly higher than the on line values at all flows. At 50 ml/s the geometric mean (SE) off line eNO was 18.7 (1.1) ppb and the on line eNO was 15.1 (1.1) ppb (p<0.0001). However, when dead space air was discarded, off line and on line values were similar: at 50 ml/s off line eNO was 17.7 (1.0) ppb and on line eNO 16.0 (1.2) ppb. There was a good agreement between off line eNO values without dead space air and on line eNO: for 50 ml/s the mean on/off line ratio was 0.95 (95% agreement limits 0.63 to 1.27). The off line eNO level at 50 ml/s in 80 children with negative questionnaires for asthma, rhinitis, and eczema was 13.6 (1.0) ppb compared with 33.3 (1.1) ppb in the remaining children with positive questionnaires on asthma and allergy and/or recent symptoms of cold (p<0.0001). CONCLUSIONS: In children, off line assessment of eNO using constant low flow sampling and excluding dead space air is feasible and produces similar results as on line assessment with the same exhalation flow rate. Both sampling methods are sufficiently sensitive to differentiate between groups of otherwise healthy school children with and without self-reported asthma, allergy, and/or colds. We propose that, for off line sampling, similar low flow rates should be used as are recommended for on line measurements.

Adolescent↗
PubMed2001

Interrupter resistance in preschool children: measurement characteristics and reference values.

There is a need for quick, reliable, and noninvasive lung function tests to assess airway obstruction in preschool children both for pediatric pulmonary care as well as for research purposes. We studied feasibility, reproducibility, and validity of measurements of the respiratory system using the interrupter technique (interrupter resistance [Rint]) and obtained reference values in children from a general population, 2 to 7 yr of age. Accuracy was studied by comparisons of Rint with plethysmographic airway resistance (Raw) in 20 patients (7 to 14 yr) with mild to severe chronic airways obstruction and was satisfactory in patients with FEV(1) > 60% predicted. The technique proved sensitive enough to detect changes in airway caliber within a small group of 12 children who developed mild respiratory tract infections. Among children from a general population, subgroups with mild respiratory symptoms or mild respiratory disease had higher mean Rint values. Airway obstruction was better detected using expiratory rather than inspiratory interruptions, both programmed at peak tidal ventilatory flow. Reproducibility within subjects was satisfactory (intraclass correlation 0.82 and 0.79). The same applied to interobserver agreement (intraclass correlation 0.98). The interrupter technique proves to be a reliable and practical test of airway function, suitable for clinical and epidemiologic studies in preschool children.

Age Factors↗
PubMed2000

Unexpected life-threatening complications in Kabuki syndrome.

Kabuki syndrome is a rare multiple congenital anomalies/mental retardation syndrome comprising a distinct facial appearance and fetal fingertip pads. We observed two patients with Kabuki syndrome and describe unusual life-threatening complications, including stenosis of the central airways (not previously reported), extrahepatic biliary atresia, and congenital diaphragmatic hernia.

Abnormalities, Multiple↗
PubMed2000

Aerosol therapy in cystic fibrosis: a survey of 54 CF centers.

Aerosol therapy has become increasingly important in the treatment of lung disease of patients with cystic fibrosis (CF). Still, many questions concerning this therapy remain unanswered. It is unclear at what age aerosol therapy should be started; which aerosolized drugs are essential in the treatment of CF lung disease; which delivery system(s) should be used; and how aerosol therapy should be timed in relation to physiotherapy. We hypothesized that large differences in aerosol treatment practices between CF centers would be present. To investigate this, we performed an observational survey to evaluate different aspects of aerosol therapy. A questionnaire was sent to 102 CF centers in 28 different countries. A completed questionnaire was returned by 54 out of 94 centers (57%). In these 54 centers, 7,324 CF patients were treated. Substantial differences were found in aerosol therapy between centers. Patients below age 1 year were not treated with any form of aerosol therapy in 10% of the centers, while 37.5% of the centers treated all of these patients. The timing of nebulization and physiotherapy varied substantially for many important and expensive drugs. We conclude that many aspects of aerosol therapy in cystic fibrosis need to be executed in a more rational and evidence-based manner than is currently the case.

Administration, Inhalation↗
PubMed2000

Cartilaginous airway wall dimensions and airway resistance in cystic fibrosis lungs.

It is not clear how airway pathology relates to the severity of airflow obstruction and increased bronchial responsiveness in cystic fibrosis (CF) patients. The aim of this study was to measure the airway dimensions of CF patients and to estimate the importance of these dimensions to airway resistance using a computational model. Airway dimensions were measured in lungs obtained from CF patients who had undergone lung transplantation (n=12), lobectomy (n=1), or autopsy (n=4). These dimensions were compared to those of airways from lobectomy specimens from 72 patients with various degrees of chronic obstructive pulmonary disease (COPD). The airway dimensions of the CF and COPD patients were introduced into a computational model to study their effect on airway resistance. The inner wall and smooth muscle areas of peripheral CF airways were increased 3.3- and 4.3-fold respectively compared to those of COPD airways. The epithelium was 53% greater in height in peripheral CF airways. The sensitivity and maximal plateau resistance of the computed dose/response curves were substantially increased in the CF patients compared to COPD patients. The changes in airway dimensions of cystic fibrosis patients probably contribute to the severe airflow obstruction, and to increased bronchial responsiveness, in these patients.

Adolescent↗
PubMed2000

Hydrogen peroxide and nitric oxide in exhaled air of children with cystic fibrosis during antibiotic treatment.

Cystic fibrosis (CF) patients characteristically have severe chronic airway inflammation associated with bacterial infection. A noninvasive marker of airway inflammation could be a useful guide to treatment of CF lung disease. The aim of this study was to assess whether measurement of hydrogen peroxide (H2O2) and nitric oxide (NO) in exhaled air can serve to monitor the effect of treatment with antibiotics in CF-children with acute infective pulmonary exacerbations. Sixteen CF-patients (mean age 12.3 yrs) with exacerbation of their lung infection were treated with intravenous antibiotics in an uncontrolled study. During treatment, H2O2 in exhaled air condensate was measured twice a week. In addition, serial NO measurements were performed in nine patients. During antibiotic treatment the median H2O2 concentration in exhaled air condensate decreased significantly from 0.28 microM (range 0.07-1.20 microM) to 0.16 microM (range 0.05-0.24 microM, p=0.002) and the mean forced expiratory volume in one second significantly increased from 55% predicted to 75% pred (p=0.001). In individual subjects, changes of H2O2 and FEV1 between pairs of serial measurements correlated weakly (p=0.08). Data on exhaled NO were inconclusive; exhaled NO did not change systematically during treatment. It is concluded that cystic fibrosis patients with an acute pulmonary exacerbation have abnormally high concentrations of hydrogen peroxide, but not of nitric oxide, in exhaled air, which decrease during intravenous antibiotic treatment. Further controlled studies should establish if exhaled hydrogen peroxide, may serve as a noninvasive parameter of airway inflammation to guide antibiotic treatment in cystic fibrosis lung disease.

Acute Disease↗
PubMed2000

Inhaled disodium cromoglycate (DSCG) as maintenance therapy in children with asthma: a systematic review.

BACKGROUND: Disodium cromoglycate (DSCG) is included in the BTS guidelines on the treatment of asthma for use in children, but is now used only infrequently. We have identified and interpreted the findings of all published randomised, placebo controlled trials of DSCG in the prophylactic treatment of children with asthma. METHODS: Several databases were searched to identify trials. Studies were included if they investigated subjects with asthma aged 0-18 years old, addressed maintenance treatment with inhaled DSCG, and were published in English. The methodological quality of the studies was assessed independently by three reviewers. The 95% confidence intervals (CI) of differences in the treatment effect for cough and wheeze between placebo and treatment with DSCG were computed. The estimates were pooled and tested for homogeneity and, to assess possible publication bias, a funnel plot was made and tested for symmetry. RESULTS: Of the 24 randomised, placebo controlled trials identified, the methodological scores varied widely. The null hypothesis of homogeneity was rejected. Under the assumption of heterogeneity the overall CI for wheeze was 0.11 to 0.26 and for cough was 0.13 to 0.27. The overall tolerance intervals (-0.11 to 0. 48 and -0.04 to 0.43 for wheeze and cough, respectively) both included zero, so it cannot be concluded that future studies will show an effect of DSCG compared with placebo. Older studies were more often in favour of DSCG. The funnel plots suggest publication bias; small studies with negative or equal outcomes are lacking. CONCLUSION: Given the apparent publication bias, the small overall treatment effect, and the tolerance interval including zero, there is insufficient evidence that DSCG has a beneficial effect as maintenance treatment in children with asthma.

Administration, Inhalation↗
PubMed2000

Adolescents in clinical remission of atopic asthma have elevated exhaled nitric oxide levels and bronchial hyperresponsiveness.

Symptoms of atopic asthma often decrease or even seem to disappear around puberty. The aim of this study was to investigate whether this so-called clinical remission is accompanied by remission of airway inflammation, since symptoms relapse in a substantial proportion of subjects later in life. To assess indicators of inflammation and/or structural damage of the airways, exhaled nitric oxide (eNO) and bronchial responsiveness to adenosine-5'-monophosphate (AMP) and methacholine (MCh) were determined in 21 subjects in clinical remission of atopic asthma. Clinical remission was defined as complete absence of symptoms of asthma without the use of any medication in the year preceding the study. Results were compared with those of 21 patients with current asthma and 18 healthy control subjects. We found significantly higher eNO values in the remission group than in healthy controls (geometric mean, 18.9 and 1.0 ppb, respectively; p < 0.001) whereas eNO values of the remission group and those of the subjects with current asthma (geometric mean, 21.9 ppb) were similar (p = 0.09). The responsiveness to both AMP and MCh of subjects in clinical remission was significantly higher as compared with responsiveness of healthy controls, and lower than responsiveness of subjects with current asthma. A significant correlation could be established between eNO and responsiveness to AMP, but not between eNO and responsiveness to MCh. The results of this study are suggestive of persistent airway inflammation during clinical remission of atopic asthma. We speculate that subclinical inflammation is a risk factor for asthma relapse later in life, and that eNO and responsiveness to both AMP and MCh can be used as different, noninvasive indices of the inflammatory process of the airways.

Adenosine Monophosphate↗
PubMed2000

Gas analysis.

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Adult↗
PubMed2000

Tumor necrosis factor-alpha enhances mRNA expression and secretion of interleukin-6 in cultured human airway smooth muscle cells.

Airway smooth muscle (ASM) is considered to be an end-target cell for the effects of mediators released during airway wall inflammation. Several reports suggest that activated ASM may be capable of generating various proinflammatory cytokines. We investigated the effects of tumor necrosis factor (TNF)-alpha, a potent proinflammatory cytokine, on cultured human ASM cells by examining the expression and release of the cytokine interleukin (IL)-6, cell proliferation, and the expression pattern of c-fos and c-jun, two nuclear proto-oncogenes constituting the activator protein-1 transcription factor. Growth-arrested cell monolayers were stimulated with human recombinant TNF-alpha in a concentration- and time-dependent manner. TNF-alpha stimulated the expression of IL-6 messenger RNA (mRNA), which was detected after 15 min, reaching a maximum at 1 h. IL-6 protein was readily detected in ASM cell-conditioned medium after 2 h of TNF-alpha stimulation. Protein levels increased in a time- and concentration-dependent manner. Release of IL-6 elicited by TNF-alpha was significantly inhibited by dexamethasone, cycloheximide, and nordihydroguaiaretic acid (NDGA). TNF-alpha did not alter DNA biosynthesis up to 48 h or cell numbers up to 120 h. Northern blot analysis of proto-oncogene expression revealed that c-fos and c-jun mRNA levels were elevated after 30 min of TNF-alpha incubation with maximum levels at 1 h and 45 min, respectively. Expression of c-fos mRNA was downregulated by NDGA. Four hours of TNF-alpha treatment resulted in translocation of c-jun immunofluorescence from the cytoplasm to the nucleus in human ASM cells. Our results suggest that despite the lack of a mitogenic response to TNF-alpha, upregulation of primary response genes in human ASM cells may account for the induction of proinflammatory cytokines, such as IL-6, in human airways.

Bronchi↗
PubMed2000

Aerosol delivery from spacers in wheezy infants: a daily life study.

The aims of this study were to assess and compare dose delivery and dose variability of pressurized metered dose inhalers (pMDI)/spacers in wheezy infants in daily life and to investigate factors influencing aerosol delivery. In an open randomized crossover study in 25 wheezy infants aged 5-26 months, a metal spacer (Nebuchamber), a detergent coated (DC) and a non-detergent coated (nonDC) plastic spacer (Babyhaler) were tested at home for 7 days each. Budesonide (200 microg b.i.d) was administered via a Nebuchamber or fluticasone (125 microg b.i.d) via a Babyhaler. Aerosol was trapped in filters, positioned between the spacer and face mask. Cooperation was scored on diary cards. Electrostatic charge (ESC) of the spacers was measured. Evaluations of the administration technique were made from video recordings. Median (range) dose delivery of the filters expressed as per cent (%) of nominal dose, was 34% (3-59), 23% (1-49), and 41% (12-55) for the Nebuchamber, nonDC-Babyhaler, and DC-Babyhaler respectively. Considerable dose variability was found, median (range) within-subject dose variability, expressed as coefficient of variation, for the Nebuchamber (49% (15-249)) was significantly higher when compared with both nonDC- (36% (12-325)) and DC-Babyhalers (27% (10-122)), for which dose variabilities were similar. Detergent coating was effective to reduce electrostatic charge, and to increase dose delivery, but had no effect on dose variability. Bad cooperation was an important cause for high dose variability for all spacers (r=0.5-0.6, p<0.02). Many mistakes were made during the administration procedure.

Aerosols↗
PubMed2000

A family with extrinsic allergic alveolitis caused by wild city pigeons: A case report.

We describe a family in which the mother died of unresolved lung disease and whose 5 children, some of whom had previous signs of asthma, were subsequently affected by extrinsic allergic alveolitis caused by contact with wild city pigeon antigens. The children received systemic corticosteroids for 1 month and inhaled steroids for 24 months, while antigen exposure was reduced as much as feasible. This was followed by a quick clinical recovery and a slow normalization of chest radiographs and pulmonary function indices, especially of diffusion capacity, during a follow-up of 24 months. Because pigeon-breeder's lung caused by free-roaming city pigeons has not been previously described, it remains unclear whether this family developed the disease because of high antigen exposure or because of increased susceptibility. None of the supposedly high-risk human leukocyte antigen types were found in the children. Whether human leukocyte antigen B7 in 1 child played a role in the course of the illness remains speculative. It is unknown to what extent pigeon-breeder's lung caused by nondomestic birds remains undetected and misdiagnosed as difficult or steroid-resistant asthma. The question remains whether free-roaming city pigeons are indeed a public health risk. We suggest that atypical outdoor antigens be considered in all patients with nonresolving chest disease or therapy-resistant asthma.

Adolescent↗
PubMed1999

Flow-dependency of exhaled nitric oxide in children with asthma and cystic fibrosis.

The concentration of nitric oxide in exhaled air, a marker of airway inflammation, depends critically on the flow of exhalation. Therefore, the aim of this study was to determine the effect of varying the flow on end-expiratory NO concentration and NO output in children with asthma or cystic fibrosis (CF) and in healthy children. Nineteen children with stable asthma, 10 with CF, and 20 healthy children exhaled from TLC while controlling expiratory flow by means of a biofeedback signal at approximately 2, 5, 10 and 20% of their vital capacity per second. NO was measured in exhaled air with a chemiluminescence analyser. Comparisons between the three groups were made by analysing the NO concentration at the endexpiratory plateau and by calculating NO output at different flows. Exhaled NO decreased with increasing flow in all children. Children with asthma had significantly higher NO concentrations than healthy children, but only at the lowest flows. Asthmatics using inhaled steroids (n=13) tended to have lower median exhaled NO than those without steroids. The slope of linearized (log-log transformed) NO/flow plots was significantly steeper in asthmatics than in healthy controls. CF patients had a significantly lower NO concentration and output over the entire flow range studied, compared to asthmatic and control subjects, with a similar NO/flow slope as control subjects. In conclusion, the nitric oxide concentration in exhaled air is highly flow-dependent, and the nitric oxide-flow relationship differs between asthmatics versus cystic fibrosis patients and control subjects. Assessment of the nitric oxide/flow relationship may help in separating asthmatics from normal children.

Asthma↗