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Biomedical subjects

K F Kerrebijn

Publications and source records attributed to K F Kerrebijn.

At least 19 recordsLinked to original sources
PubMed1994

Bradykinin-induced contraction of human peripheral airways mediated by both bradykinin beta 2 and thromboxane prostanoid receptors.

Bradykinin (BK) induces bronchoconstriction in asthmatic but not in normal individuals. Studies in vivo in the human suggest that BK causes cholinergic nerve activation, release of prostanoids, and local axon reflexes with release of tachykinins in the airways. To determine the mechanisms of BK-induced airway narrowing, we investigated the effects of epithelium removal, inhibition of the enzymes neutral endopeptidase (NEP) and cyclooxygenase, and blockade of neural conductance with tetrodotoxin (TTX) on BK-induced responses of human isolated peripheral airways. Responses to BK were recorded from airways with spontaneous intrinsic tone and from airways precontracted with methacholine. Furthermore, we measured the BK-induced release of the prostanoids PGE2, PGI2, and TXA2 from airways with and without epithelium in the absence and presence of indomethacin by radioimmunoassay. Finally, we examined the effect of the bradykinin beta 2 receptor antagonist Hoe 140 and the thromboxane prostanoid (TP) receptor blocking drug GR32191 on BK-induced responses. BK contracted intact and epithelium-denuded airways with spontaneous intrinsic tone, whereas precontracted airways either relaxed or contracted to BK. Removal of the epithelium increased the sensitivity to BK sevenfold without changing the direction of the response. The NEP inhibitor phosphoramidon tended to increase the sensitivity to BK (NS) and did not change the direction of the response. Both contractile and relaxation responses to BK and the release of the prostanoids PGE2, PGI2, and TXA2 by the airway tissues were largely inhibited by indomethacin, whereas TTX had no effect. PGE2, PGI2, and TXA2 were released by both intact and epithelium-denuded airways.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Remission of childhood asthma after long-term treatment with an inhaled corticosteroid (budesonide): can it be achieved? Dutch CNSLD Study Group.

This study was undertaken in order to determine whether long-term treatment with inhaled corticosteroid can induce a remission in childhood asthma, and to decide when stabilization of airway responsiveness occurred. We therefore carried out, an extended follow-up of 28-36 months in one of two groups of children who participated in a long-term intervention study. This former study had shown that long-term (median follow-up 22 months) treatment with inhaled corticosteroid plus beta 2-agonist improves symptoms, airway calibre and airway responsiveness in children with asthma, compared with beta 2-agonist alone. On treatment with inhaled corticosteroid plus beta 2-agonist, airway calibre did not further improve after 4 months, whereas the provocative dose of histamine which causes a 20% fall in forced expiratory volume in one second (PD20) histamine showed gradual improvement without reaching an apparent plateau. Remission was defined as being symptom free during any 8 month period. Of the 58 children originally randomized to receive 0.2 mg salbutamol, plus 0.2 mg budesonide, t.i.d., five children withdrew: three due to lack of motivation, one for psychological reasons, and one due to a deterioration of asthma. One patient was hospitalized because of an asthma exacerbation. Airway calibre showed no improvement after 4 months up to 36 months. Mean PD20 histamine stabilized after 20 months at 2.1 doubling doses above baseline, but at a subnormal level of 80 micrograms. Symptoms improved during the first 18 months, and may have been improving further, but slowly, during the period between 18 and 36 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Measurement of bronchial responsiveness in young children: comparison of transcutaneous oxygen tension and functional residual capacity during induced bronchoconstriction and -dilatation.

Demonstration of an increased bronchial responsiveness in preschool children may support the diagnosis of asthma. Most young children cannot perform routine lung function tests. Transcutaneous PO2 (PtcO2) measurement has been applied successfully in young children, and changes in PtcO2 have been shown to correlate well with changes in forced expiratory volume in 1 second (FEV1) during bronchoprovocation testing with methacholine. PtcO2 is, however, an indirect measure of the effect of inhaled spasmogens. As functional residual capacity (FRC) can also be measured by helium dilution spirometry in preschool children, we compared PtcO2 and FRC during methacholine inhalation challenges and after inhaled terbutaline, in order to determine whether FRC is useful as a more direct measure of induced bronchoconstriction and -dilatation than PtcO2. We studied 41 allergic asthmatic children (mean age, 5.2 years) who underwent a methacholine bronchoprovocation test; 38 children received terbutaline 1 h after the final methacholine dose. The provocative concentration of methacholine that caused a 20% decrease of PtcO2 was determined, and changes in FRC and PtcO2 after each methacholine dose step were compared. Similarly, changes in PtcO2 and FRC before, and 15 and 30 min after, terbutaline were compared. All children had a drop in PtcO2 after increasing doses of methacholine; a 20% change was reached in 38 patients. Mean FRC values increased significantly but variably with increasing doses of methacholine, and changes in PtcO2 and FRC did not correlate. After terbutaline, PtcO2 increased slightly but significantly, and FRC again varied unpredictably. In a separate group of 11 children, the effect of terbutaline was assessed directly after the final methacholine dose, when significant bronchoconstriction was still present.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗
PubMed1992

The perfused human bronchiolar tube characteristics of a new model.

Strips or rings of airway tissue are often used to study contractile responses of human airways in vitro. These preparations have the disadvantage that it is impossible to deliver stimuli selectively to the mucosal or serosal surface. Hence, they allow only for a limited evaluation of the modulatory role of the airway epithelium. We developed an in vitro model that allows independent stimulation from either the serosal or the mucosal side of human peripheral airways. Segments of human peripheral airways were perfused with a Krebs solution at a constant pressure, and responsiveness was measured as a change in flow rate. Pressure/flow relationships indicated laminar flow over a wide pressure range, and a working pressure of 6 cm H2O was chosen because this is a physiological transpulmonary pressure. When stepwise stretching the airway to 180% of its length, we noted an increase in baseline flow and a decrease in flow reduction after methacholine 10(-5) M. At 140% of the length, accurate and reproducible measurements of the sensitivity (EC50) to methacholine were obtained, and airway closure did not occur. A one-way analysis of variance (ANOVA) revealed that the between-patients differences accounted for 91% of the total variability for -log EC50. We conclude that this in vitro model offers interesting possibilities for evaluating the modulatory effects of the human airway epithelium. In addition, the model provides the opportunity to study human small-airway mechanical properties and secretory functions.

Adult↗
PubMed1992

Assessment of bronchodilatation after spontaneous recovery from a histamine challenge in asthmatic children.

BACKGROUND: It would be convenient to be able to measure airway responsiveness to histamine and to bronchodilator drugs on the same day, but whether this can be done reliably is unknown. METHODS: The effect of a prior histamine challenge on the bronchodilator response to salbutamol after spontaneous recovery of FEV1 to 95% of the prechallenge level was studied in two groups of asthmatic children. Fourteen children inhaled 400 micrograms salbutamol after spontaneous recovery from a histamine challenge, followed by a further 100 micrograms salbutamol 20 minutes later. In a second group of eight asthmatic children the study was repeated with 800 micrograms salbutamol, followed by a further 200 micrograms 20 minutes later. RESULTS: After histamine challenge FEV1 returned to baseline in 70 minutes or less on all occasions. The FEV1 20 minutes after 400 micrograms salbutamol was significantly lower after the histamine challenge than on the control day. After the further 100 micrograms salbutamol FEV1 values were similar after the histamine challenge and on the control day. FEV1 values after 800 micrograms salbutamol and the further 200 micrograms dose were not influenced by a prior histamine challenge. CONCLUSIONS: In children with stable asthma in whom FEV1 has returned to baseline after a histamine challenge the FEV1 achieved after 800 micrograms salbutamol is not affected by the histamine challenge. Histamine and bronchodilator responsiveness can thus be assessed reliably on the same day in patients with stable asthma. This has clear advantages for patient care.

Adolescent↗
PubMed1992

Effects of 22 months of treatment with inhaled corticosteroids and/or beta-2-agonists on lung function, airway responsiveness, and symptoms in children with asthma. The Dutch Chronic Non-specific Lung Disease Study Group.

In a randomized double-blind multicenter clinical study, 116 children with asthma were randomly assigned to treatment with an inhaled beta-2-agonist (salbutamol 0.2 mg) plus an inhaled corticosteroid (budesonide 0.2 mg) three times a day (BA+CS) or to an inhaled beta-2-agonist (salbutamol 0.2 mg) plus a placebo three times a day (BA+PL). After a median follow-up time of 22 months, 26 patients receiving BA+PL (45%) had withdrawn from randomized treatment, mainly because of asthma symptoms, compared with three withdrawals in the patients receiving BA+CS (p less than 0.0001). The FEV1, expressed as a percentage of the predicted value for age, sex, and height, showed an absolute increase of 7.0% after 2 months of BA+CS compared with a decrease of 4.0% after 2 months of BA+PL. This 11% difference in percent predicted FEV1 (95% confidence interval, 7 to 15%; p less than 0.0001) was then maintained after a median follow-up period of 22 months. Postbronchodilator FEV1 showed an absolute increase of 3.7% predicted within 2 months in patients receiving BA+CS and an absolute decrease of 1.1% predicted in children receiving BA+PL (p = 0.0005). Thereafter, this difference between the two treatment groups was maintained. Average peak expiratory flow rate (PEFR) increased from baseline by 36.6 L/min in the BA+CS group compared with 3.7 L/min in the BA+PL group (p = 0.003). This difference then remained for the median follow-up time of 22 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Lung volumes measured by the forced rebreathing technique in children with airways obstruction.

Forced rebreathings may recruit trapped gas into the mixing process. Therefore, we assessed the validity and reproducibility of measurements of residual volume (RVN2) by forced rebreathing in a closed circuit using N2 as indicator gas (N2FR) in children with airways obstruction. Validity was studied from measurements of RV obtained by N2FR, by helium dilution during resting ventilation, and by body plethysmograph at low panting frequency in young patients (8-18 yrs, 13 with asthma, forced expiratory volume in one second (FEV1) 93.0 +/- 22.8% pred; 12 with cystic fibrosis (CF), FEV1 80.4 +/- 16.4% pred). Reproducibility of RVN2 was assessed from duplicate measurements in 73 patients with asthma before and after bronchodilation (FEV1 81.4 +/- 13.7 and 99.6 +/- 11.5% pred, respectively), and in nine patients with CF; the total lung capacity (TLC) was unaffected by bronchodilation; 3,797 +/- 830 ml and 3,807 +/- 843 ml, respectively. Gas dilution methods gave comparable results in all subjects but gave lower values than plethysmography in patients with cystic fibrosis. Reproducibility was satisfactory, median differences between duplicate measurements of RVN2 and TLCN2 varying between 13 and 46 ml, respectively. We conclude that N2FR is quickly performed and well-tolerated. Lung volumes are highly reproducible and agree well with those obtained with the helium dilution method. Deep inspirations do not seem to overcome gas trapping in patients with CF.

Adolescent↗
PubMed1992

Changes of nebulizer output over the years.

The effects of long-term use and of cleaning on the output of 30 specimens of DeVilbiss 646 nebulizers were investigated in order to assess their influence on outcome and interpretation of inhalation provocation tests. Output was assessed in a standardized manner based on weight loss on four occasions one year apart. Output was highly reproducible (intraclass correlation greater than or equal to 0.90), and varied considerably between nebulizers, necessitating calibration at least once. Inadequate cleaning diminished nebulizer output by a factor of two (p less than 0.01), while long-term use was associated with a moderate increase in output of 0.28 mg.yr-1 (p less than 0.0001). Bronchial responsiveness can be underestimated by about one doubling dose due to inadequate cleaning, while interchanging nebulizers can lead to overestimation or underestimation by up to one doubling dose. With proper care the increase in output due to wear has no consequences for clinical practice, or for longitudinal studies.

Bronchial Provocation Tests↗
PubMed1991

Comparison of FEV1 and transcutaneous oxygen tension in the measurement of airway responsiveness to methacholine.

The measurement of airway responsiveness in preschool children is hampered by the fact that most tests of airway caliber are difficult to carry out at a young age. Patient cooperation is only needed to a limited extent when transcutaneous oxygen tension (PtcO2) is used as an indicator of airway obstruction following bronchial provocation. In 51 children, aged 6-14 years with asthma we have measured PtcO2 and forced expiratory volume in 1 second (FEV1) concurrently after bronchial provocation, using increasing doses of methacholine administered with a De Villbiss 646 nebulizer and a French-Rosenthal dosimeter. The shapes of the dose-response curves to PtcO2 and FEV1 show a close similarity. After methacholine challenge, the decrease in PtcO2 correlates highly with the decrease in FEV1. We conclude that in children a 20% decrease in PtcO2 can be used as a sensitive indicator of airway narrowing after methacholine challenge.

Asthma↗
PubMed1991

Effects of hyperosmolarity on human isolated central airways.

1. We studied the effect of hyperosmolarity on human isolated airways because a better understanding of the effect of hyperosmolarity on the human airway wall may improve insight into the pathophysiology of hyperosmolarity-induced bronchoconstriction in asthma. 2. In cartilaginous bronchial rings dissected from fresh human lung tissue, hyperosmolar krebs-Henseleit buffer (450 mosM, extra sodium chloride added) evoked a biphasic response: a rapid relaxation phase (peak after 5.0 +/- 0.3 min) followed by a slow contraction phase (peak after 25.4 +/- 0.8 min). 3. With the histamine (H1) receptor antagonist mepyramine, the contraction phase was reduced to 41.2% of the control value (P less than 0.001), with atropine to 50.0% (P less than 0.01), with the local anaesthetic lignocaine to 48.7% (P less than 0.05) and with mepyramine together with atropine to 19.2% (P less than 0.001). 4. With the inhibitor of neutral metalloendopeptidase, phosphoramidon, the contraction phase increased to 128.0% of the control value (P less than 0.05) and after removal of the epithelium to 131.8% (P less than 0.05). 5. Indomethacin, the leukotriene C4/D4 (LTC4/D4) antagonist FPL 55712 or the blocker of nerve conduction, tetrodotoxin, had no effect on the contractile phase. 6. The relaxation phase was not altered by any of these drugs nor by epithelial denudation. The relaxation phase was also unchanged in the presence of alpha-chymotrypsin, which degrades muscle relaxing peptides such as vasoactive intestinal peptide. 7. Hyperosmolar buffer slightly increased the sensitivity and maximal response to methacholine as well as the cholinergic twitch to electric field stimulation. 8. We conclude that hyperosmolarity releases acetylcholine, histamine and neuropeptides in the human airway wall in sufficient quantities to contract airway smooth muscle. This release itself or its effect on airway muscle is modulated by the airway epithelium. The mechanism of the relaxation phase may be an unknown smooth muscle relaxing substance or a direct effect on the airway muscle, related to ion fluxes.

Acetylcholine↗
PubMed1991

Effect of cooling on responses of isolated human airways to pharmacologic and electrical stimulation.

We studied the effect of cooling on the responses of isolated human airways to the beta-agonist isoproterenol, the alpha/beta-agonist norepinephrine in the presence of the beta-blocker timolol, methacholine, leukotriene C4 (LTC4), and histamine. In addition, the effect of cooling on baseline airway tone and responses to electric field stimulation (EFS) was studied. At 27 degrees C the sensitivity (-logEC50) and maximal response to isoproterenol were unchanged. No measurable response was found to alpha-adrenergic stimulation with norepinephrine + timolol either before or during cooling. At 27 degrees C and 21 degrees C the sensitivity and maximal contraction to methacholine and LTC4 as well as the contraction to a single dose of histamine were reduced. Cooling diminished baseline airway tone. EFS produced a rapid cholinergic contraction followed by a deflection below baseline and a sustained noncholinergic contractile response, which was substantially reduced by the LTC4/D4 receptor antagonist FPL 55712 (11.5 microM) at all three temperatures. Cooling decreased the cholinergic response to EFS and increased the sensitivity to EFS-induced relaxation. In contrast, the sustained noncholinergic contractile response to EFS was not changed, suggesting that cooling facilitates the synthesis of LTC4/D4 that follows EFS and/or inhibits its inactivation. We conclude that in nonasthmatic, isolated human airways slow cooling of the airway wall down to 21 degrees C does not cause bronchoconstriction and does not increase the responsiveness to contractile or relaxing agonists. However, cooling increases the sensitivity to EFS-induced relaxation and might facilitate the accumulation of leukotriene C4/D4 in the airway wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effects of zymosan-activated human granulocytes on isolated human airways.

In asthma a temporal association exists between the late allergic reaction (LAR), the influx of granulocytes into the airway wall, and an increase in bronchial responsiveness. We therefore tested the hypothesis that activated human granulocytes constrict isolated human airways and increase their sensitivity to cholinergic stimuli. Bronchial rings were dissected from 23 lung tissue specimens collected at thoracotomy and studied isotonically in organ baths. Airways were incubated with 1, 2, 5, 10, or 20 x 10(6) granulocytes from normal or atopic donors. Activation of the cells with serum-treated zymosan (STZ, 0.2 mg/ml), which itself did not alter baseline airway caliber, resulted in a bronchoconstriction proportional to the number of zymosan-activated granulocytes (ZAG) present (rs = 0.79, p less than 0.001). This contraction was reduced by about 70% with the leukotriene C4/D4 receptor antagonist FPL 55712 (11.5 microM; p less than 0.001) or with the lipoxygenase inhibitor nordihydroguaiaretic acid (10 microM; p less than 0.001). The scavengers of activated oxygen molecules superoxide dismutase (300 U/ml) and bovine catalase (5,000 U/ml), the cyclooxygenase inhibitor indomethacin (10 microM), or the histamine (H1) receptor antagonist mepyramine (2.8 microM) had no effect. Granulocyte suspensions from atopic donors contained more eosinophils (p less than 0.001), and the magnitude of the contraction to 10 x 10(6) ZAG was related to the proportion of eosinophils (rs = 0.66, p less than 0.01). The sensitivity of the airways to methacholine was unchanged in the presence of 1, 2, or 5 x 10(6) ZAG and decreased with 10 or 20 x 10(6) ZAG (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The increased responsiveness to inhaled methacholine in asthma: combination of causative factors.

In asthma the dose-response curve to inhaled methacholine (MCh) is shifted leftwards and shows an increased slope and maximum. Two factors might contribute to the different form and position of this curve: (1) mediator-induced airway muscle hypersensitivity and (2) thickening of the airway wall. We attempted to estimate the effect of a combination of these two factors on the increase in airway resistance of a single isolated human airway to increasing concentrations of MCh. The result suggests that mediator-induced hypersensitivity to cholinergic stimuli may explain a small part of the leftward shift of the asthmatic dose-response curve to MCh, especially at lower levels of bronchoconstriction, and that increased thickness of the airway wall may be more important for the increased slope and maximum of the asthmatic dose-response curve.

Airway Resistance↗
PubMed1991

Control of airway caliber by autonomic nerves in asthma and in chronic obstructive pulmonary disease.

Autonomic nerves can influence airway caliber via their effects on airway smooth muscle, bronchial vessels, and mucous glands and may therefore contribute to airway narrowing in asthma or in chronic obstructive pulmonary disease (COPD). Human lungs receive cholinergic, noradrenergic, and peptidergic efferents and several types of afferents. Cholinergic nerve activity contributes to airway narrowing both in asthma and in COPD. Reflex vagal activity may be enhanced because of epithelial damage and exposition of sensory nerve endings to nonspecific irritants. Other possible mechanisms include defects in prejunctional receptors that inhibit acetylcholine release, several postjunctional factors that nonspecifically enhance the effect of a given degree of cholinergic muscle contraction on airway caliber, and interactions between inflammatory mediators and the cholinergic system. The main direct bronchodilating nerve activity in human lungs is nonadrenergic, and scanty data suggest that nonadrenergic inhibitory nerve activity may be variably reduced in asthmatics. Human airway muscle virtually lacks adrenergic innervation, but adrenergic nerves may influence airway caliber by acting on bronchial vessels, mucous glands, and parasympathetic nerves and ganglia. The response of asthmatic airways to beta-agonists seems intrinsically normal, but it may be reduced during severe asthma attacks. There are no convincing data that abnormal adrenergic control is present in the airways of patients with COPD. The physiologic relevance of excitatory neuropeptides in sensory nerves in human airways is uncertain. Tachykinins have proinflammatory and spasmogenic properties and are therefore of potential interest as a factor in the pathogenesis of obstructive airway disease. In conclusion, the data presently available support an abnormal autonomic control of the airways in asthma but not in COPD.

Asthma↗
PubMed1990

Activated human granulocytes contract isolated human airways.

Human granulocytes activated with serum treated zymosan (0.2 mg/ml) contract isolated human airways. The magnitude of the contraction depends on the number of granulocytes and the proportion of eosinophils among the granulocytes. The contraction is blocked by a leukotriene C4/D4 (LTC4/D4) receptor antagonist and by inhibition of lipoxygenase. This suggests that eosinophils rather than neutrophils are implicated in this response, which seems to be caused by LTC4/D4.

Bronchi↗
PubMed1990

Additive effect of epithelial denudation and low levels of inflammatory mediators on the sensitivity of isolated human airways to methacholine.

The presence of low concentrations of histamine or the stable thromboxane analogue U46619 and the removal of the epithelium separately and addictively increase the sensitivity of isolated human airways to methacholine. This raises the possibility that these factors play a role in the pathogenesis of bronchial hyperresponsiveness to inhaled methacholine in asthma.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗