ln this thesis several aspects of the contribution of the eosinophil to the pathophysiology of childhood asthma have been studied and described. ln the 1st chapter the pathophysiology of asthma is discussed, with special emphasis on the contribution of the eosinophil.ln the 2nd chapter we describe a possible relationship between age and both IgE and the number of eosinophils in childhood asthma. ...

Zie: Summary

Hoekstra, Maarten Otto,

Hoekstra, Maarten Otto

NARCIS 

Eosinophils in childhood asthma

University of Groningen

   University of GroningenEosinophils in childhood asthmaHoekstra, Maarten OttoIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1996Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Hoekstra, M. O. (1996). Eosinophils in childhood asthma. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 12-11-2019SummarySutvtuenvln this thesis several aspects of the contribution of the eosinophil to thepathophysiology of childhood asthma have been studied and described.ln the Ist chapter the pathophysiology of asthma is discussed, with specialemphasis on the contribution of the eosinophil.lnthe 2nd chapter we describe a possible relationship between age and both IgEand the number of eosinophils in childhood asthma. From previous clinical obser-vations we hypothesized that IgE would increase and the number of eosinophilswould decrease with age. In a retrospective study design we found that IgE in-creased and the number of eosinophils decreased with age in the population of182 newly admitted children with asthma. This age-dependency of IgE and thenumber of eosinophils was less pronounced than we expected. This differencein results can possibly be due to selection of a group of children with considerableheterogeneity in the presence of atopy. Another explanation could be a differencein the severity of asthma of the population studied. Thirdly, we used a regressionanalysis to analyze the data, whereas other investigators compared mean valuesof IgE and eosinophils between artificially-created age-categories. The small effectof age on IgE and eosinophils in our population of asthmatic children is not easilyexplained by the concept of an imbalance in Thl/Th2-cell produced cytokinesas a fundamental mechanism for the pathophysiology of atopic asthma.In the 3rd chapter we describe the cytokine pattern produced by mononuclearcells in peripheral blood of 22 children with asthma compared with 17 healthynon-atopic controls. Consistent with findings reported in snrdies performed inasthmatic adults, we expected to find aTta-cell pattern of cytokines in asthmaticchildren. The concentrations of Interleukin-4 (IL-4), Interferon-7 (IFN-,y) andInterleukin-5 were measured in serum and supernatants of cultures of peripheralblood mononuclear cells (PBMC). Production of IFN-7 in supernatants of culturesof stimulated PBMC's lower and the ratio of IL-4/IFN-7 higher in the asthmaticchildren compared with the controls (all differences were significant). The numberof eosinophils were related to the concentration of IL-4 and IL-5 in supernatantsof cultures of stimulated PBMC's. Lung function (FEV,) andIgE were inverselyrelated to IFN-7 in supernatants of cultures of stimulated PBMC. We concludedthatthe pattern of cytokines produced by PBMC of children with moderate stable145activity, resulting in a dominance of TM-cell activity. The findings in this studyindicate the importance of IFN-1with respect to the pathophysiology of childhoodasthma. The cytokine pattern found suggests the existence of insufficient Th I -cellactivity in children with asthma, which could be compatible with a Th2-celldominance.lnthe 4th chapter we describe the degree of in vivo'priming' of the eosinophilsin the peripheral blood, measured as the percentage of hypodense eosinophils,which was increased in asthmatic children compared with healttry non-atopiccontrols. In asthmatic adults it was found that the sedimentation procedure (bywhich the leukocytes are separated from the erythrocytes) induced an increasetn in vitro percentage of hypodense osinophils in the peripheral blood. Wedetermined a density profile of eosinophils in l8 children with allergic asthmaand in l5 healthy non-atopic ontrols. Density was determined using two differentprocedures: erythrocytes were removed by isotone lysis in the first procedure(the direct method) and by the use of dextran sedimentation in the secondprocedure (dextran method). Results showed an increase in the ln vitro percentageof hypodense eosinophils only if the dextran method was used to remove theerythrocytes . The in vitro percentage of hypodense osinophils was significantlyrelated with the number of eosinophils and with lung function when the directmethod was used. We concluded that an increased percentage of hypodense osin-ophils can be generated in vitro by dextran sedimentation. which suggests a'primed' state of eosinophils in vivo in patients with astllna.ln the Sth chapter we describe the value of serum ECP and EDN (as in vitroparameters of eosinophil activation) and urinary EDN (EDN,) in the diagnosisof pediatric asthma. We determined the number of eosinophils, serum ECP andEDN and EDN" in 22 chlldren with stable allergic moderate asthma, aged 4 to14 years, and in 17 non-atopic healthy controls. Lung function tests (FEV, andPC"o) were measured in children older than 8 years of age. Children younger than8 years of age recorded symptoms and peak flow (PEFR) values during I week.At the time of the study the asthmatic hildren were free of symptoms. No signifi-cant difference in PEFR values was found between the asthmatic children andcontrols. The FEV, was significantly lower in asthmatic hildren compared witlrcontrols. The number of eosinophils, serum ECP and EDN and EDN" were signi-146Summaryficantly higher in the asthmatic children compared with the controls. Serum ECP,and EDN and EDN" were related with the number of eosinophils. The numberof eosinophils and EDN" were significantly related to the nocturnal PEFR andto the FEV,. In conclusion, our results suggest that the determination of the serumand urine concentrations of eosinophil derived proteins can be determined in steadof the number of eosinophils to diagnose asthma in children. Especially urinaryconcentration of EDN" might be an important alternative and non-invasive toolin young asthmatic children.In the 6th chapter we describe the effect of treatment with FP on severalparameters of mast cell and on in vitro parameters of eosinophil activation in ttrethe study design as described in chapter 7. Because FP is een anti-inflammatorydrug, we expected to see a change in inflammatory parameters during treatmentwith FP. As a parameter of mast cell activation N"-methyl-histamine and as lnvitro pararneters of eosinophil activation serum ECP and EDN and urinary EDN(EDN,) were determined. In the FP group, we observed a significant decreasein symptoms and bronchial hyperreactivity. (Chapter 7) We found no differencebetween the two treatrnent groups in any of the parameters measured uring ueat-ment. Also, we also did not find a significant change in any of the laboratoryparameters within the FP group. The only parameter that tended to decrease wasEDN,, with a p-value < 0.07. We conclude that treatrnent of children with stable,moderate asthma with FP l00pg bd has a local rather than a systemic anti-inflammatory effect. Our results warrant further investigation of EDN" as apossible parameter to monitor inflamrnation.Inthe 7th chapterwe describe effects and side-effects of treatment with a recentlydeveloped inhaled corticosteroid, fluticasone propionate (FP), in 35 children withstable, moderate asthma, in a double blind placebo-controlled trial. After thetreatment period there was a follow-up period of 4 weeks during which onlybronchodilators were allowed. At home symptoms of asthma, the use of Br-mimetics and peak expiratory flow (PEFR) were registrated in a diary twice daily.Each month, lung function, bronchial hyperresponsiveness (PCrn-histamine) andreversibility to Br-mimetics were detennined. We found that during treatrnentwheezing decreased and all PEFR values increased in the FP group. FEV,increased, PCro-histamine and reversibility decreased in the FP group. All theobserved changes were significant, with exception of the change in nocturnalPEFR. The effect of FP on symptoms and lung function were transient, sincet47Chapter 9four weeks after cessation of FP, all parameters had returned to pre-treatrnentvalues. Side-effects regarding influence of FP on the hypothalamus-pituitary-adrenal axis (HPA-axis) were measured as serum and urinary cortisol concen-tration under fasting conditions. During treatment serum cortisol did not changeand urinary cortisol significantly decreased in the FP group' only when the de-crease was compared with anunexplained increase in the placebo group. we con-clude that FP 100 pg bd is effective in children with moderate stable asthma' Withrespect to side effects, additional studies are necessary to exclude suppressionof the HPA-axis during treatrnent with FP 100'pg bd'Inthe 8rh chapterwediscuss the contribution of the studies presented in this thesisto the pathophysiology of asthma and possible issues for future research, emergingfrom this thesis.r48

ARTS repository - University of Groningen

   University of GroningenEosinophils in childhood asthmaHoekstra, Maarten OttoIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1996Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Hoekstra, M. O. (1996). Eosinophils in childhood asthma. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 08-09-2023Stellingen behorende bij het proefschrift van Maarten Otto Hoekstra Eosinophils in childhood asthma 1. 'Priming' van eosinofiele leucocyten kan ge'induceerd worden door het scheiden van erythrocyten en leucocyten in vitro met behulp van dextran. (Dit proefschrift) 2. Eosinofiele granulocyten van kinderen met een stabiel, matig ernstig astma zijn, gezien hun !age dichtheid, 'geprimed' in vivo. (Dit proefschrift) 3. De samenstelling van interleukines in het supernatant van kweken van gestimuleerde mononucleaire cellen van kinderen met astma suggereert het bestaan van een dysfunctie van de T-helper-1-cellen. (Dit proefschrift) 4. Het gebruik van de bepaling van serum ECP bij de monitoring van kinderen met astma, is onvoldoende door wetenschappelijk onderzoek onderbouwd. 5. De niet-invasieve bepaling van EON in de urine voor de monitoring van astma bij kinderen dient verder te worden onderzocht. (Dit proefschrift) 6. Voordat gesteld kan worden dat fluticasone propionaat bij kinderen met astma minder kans geeft op bijwerkingen dan de bestaande inhalatiecorticostero'iden, dient de 'pulmonale resorptie' van dit medicament eerst verder te worden onderzocht. 7. Het tijdrovend werk van het maken van een differentiaal diagnose blijkt in de praktijk een tijdsbesparende investering. 8. Specialistische laboratorium diagnostiek is alleen zinvol als de a priori kans op de te testen aandoening groot is. 9. In ervaren handen heeft het verrichten van flexibele bronchoscopie bij kinderen door een kinderarts in samenwerking met een anaesthesist een verwaarloosbaar complicatierisico. 10. Hoewel de grootste problemen van veel dokters tijdproblemen en geen geld­problemen zijn, wordt veelvuldig de indruk gewekt, dat het net andersom is. 11. De mening dat een goede assistent een dokter is, die ook na de werktijd nog in het ziekenhuis aanwezig is, dient kritisch te worden beschouwd. 12. Het probleem van het overbelaste wegennet in Nederland kan slechts worden opgelost, indien de kosten van het autorijden fors verhoogd worden. 13. Het principe van 'loon naar prestatie', dat menigeen aanspreekt, is in de praktijk nauwelijks uitvoerbaar, daar verschillende prestaties moeilijk te vergelijken zijn. 

Dutch

University of Groningen Research Database

  
 University of Groningen
Eosinophils in childhood asthma
Hoekstra, Maarten Otto
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from
it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date:
1996
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Hoekstra, M. O. (1996). Eosinophils in childhood asthma s.n.
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the
author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately
and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the
number of authors shown on this cover page is limited to 10 maximum.
Download date: 11-02-2018
Summary
Sutvtuenv
ln this thesis several aspects of the contribution of the eosinophil to the
pathophysiology of childhood asthma have been studied and described.
ln the Ist chapter the pathophysiology of asthma is discussed, with special
emphasis on the contribution of the eosinophil.
lnthe 2nd chapter we describe a possible relationship between age and both IgE
and the number of eosinophils in childhood asthma. From previous clinical obser-
vations we hypothesized that IgE would increase and the number of eosinophils
would decrease with age. In a retrospective study design we found that IgE in-
creased and the number of eosinophils decreased with age in the population of
182 newly admitted children with asthma. This age-dependency of IgE and the
number of eosinophils was less pronounced than we expected. This difference
in results can possibly be due to selection of a group of children with considerable
heterogeneity in the presence of atopy. Another explanation could be a difference
in the severity of asthma of the population studied. Thirdly, we used a regression
analysis to analyze the data, whereas other investigators compared mean values
of IgE and eosinophils between artificially-created age-categories. The small effect
of age on IgE and eosinophils in our population of asthmatic children is not easily
explained by the concept of an imbalance in Thl/Th2-cell produced cytokines
as a fundamental mechanism for the pathophysiology of atopic asthma.
In the 3rd chapter we describe the cytokine pattern produced by mononuclear
cells in peripheral blood of 22 children with asthma compared with 17 healthy
non-atopic controls. Consistent with findings reported in snrdies performed in
asthmatic adults, we expected to find aTta-cell pattern of cytokines in asthmatic
children. The concentrations of Interleukin-4 (IL-4), Interferon-7 (IFN-,y) and
Interleukin-5 were measured in serum and supernatants of cultures of peripheral
blood mononuclear cells (PBMC). Production of IFN-7 in supernatants of cultures
of stimulated PBMC's lower and the ratio of IL-4/IFN-7 higher in the asthmatic
children compared with the controls (all differences were significant). The number
of eosinophils were related to the concentration of IL-4 and IL-5 in supernatants
of cultures of stimulated PBMC's. Lung function (FEV,) andIgE were inversely
related to IFN-7 in supernatants of cultures of stimulated PBMC. We concluded
thatthe pattern of cytokines produced by PBMC of children with moderate stable
145
activity, resulting in a dominance of TM-cell activity. The findings in this study
indicate the importance of IFN-1with respect to the pathophysiology of childhood
asthma. The cytokine pattern found suggests the existence of insufficient Th I -cell
activity in children with asthma, which could be compatible with a Th2-cell
dominance.
lnthe 4th chapter we describe the degree of in vivo'priming' of the eosinophils
in the peripheral blood, measured as the percentage of hypodense eosinophils,
which was increased in asthmatic children compared with healttry non-atopic
controls. In asthmatic adults it was found that the sedimentation procedure (by
which the leukocytes are separated from the erythrocytes) induced an increase
tn in vitro percentage of hypodense osinophils in the peripheral blood. We
determined a density profile of eosinophils in l8 children with allergic asthma
and in l5 healthy non-atopic ontrols. Density was determined using two different
procedures: erythrocytes were removed by isotone lysis in the first procedure
(the direct method) and by the use of dextran sedimentation in the second
procedure (dextran method). Results showed an increase in the ln vitro percentage
of hypodense eosinophils only if the dextran method was used to remove the
erythrocytes . The in vitro percentage of hypodense osinophils was significantly
related with the number of eosinophils and with lung function when the direct
method was used. We concluded that an increased percentage of hypodense osin-
ophils can be generated in vitro by dextran sedimentation. which suggests a
'primed' state of eosinophils in vivo in patients with astllna.
ln the Sth chapter we describe the value of serum ECP and EDN (as in vitro
parameters of eosinophil activation) and urinary EDN (EDN,) in the diagnosis
of pediatric asthma. We determined the number of eosinophils, serum ECP and
EDN and EDN" in 22 chlldren with stable allergic moderate asthma, aged 4 to
14 years, and in 17 non-atopic healthy controls. Lung function tests (FEV, and
PC"o) were measured in children older than 8 years of age. Children younger than
8 years of age recorded symptoms and peak flow (PEFR) values during I week.
At the time of the study the asthmatic hildren were free of symptoms. No signifi-
cant difference in PEFR values was found between the asthmatic children and
controls. The FEV, was significantly lower in asthmatic hildren compared witlr
controls. The number of eosinophils, serum ECP and EDN and EDN" were signi-
146
Summary
ficantly higher in the asthmatic children compared with the controls. Serum ECP,
and EDN and EDN" were related with the number of eosinophils. The number
of eosinophils and EDN" were significantly related to the nocturnal PEFR and
to the FEV,. In conclusion, our results suggest that the determination of the serum
and urine concentrations of eosinophil derived proteins can be determined in stead
of the number of eosinophils to diagnose asthma in children. Especially urinary
concentration of EDN" might be an important alternative and non-invasive tool
in young asthmatic children.
In the 6th chapter we describe the effect of treatment with FP on several
parameters of mast cell and on in vitro parameters of eosinophil activation in ttre
the study design as described in chapter 7. Because FP is een anti-inflammatory
drug, we expected to see a change in inflammatory parameters during treatment
with FP. As a parameter of mast cell activation N"-methyl-histamine and as ln
vitro pararneters of eosinophil activation serum ECP and EDN and urinary EDN
(EDN,) were determined. In the FP group, we observed a significant decrease
in symptoms and bronchial hyperreactivity. (Chapter 7) We found no difference
between the two treatrnent groups in any of the parameters measured uring ueat-
ment. Also, we also did not find a significant change in any of the laboratory
parameters within the FP group. The only parameter that tended to decrease was
EDN,, with a p-value < 0.07. We conclude that treatrnent of children with stable,
moderate asthma with FP l00pg bd has a local rather than a systemic anti-
inflammatory effect. Our results warrant further investigation of EDN" as a
possible parameter to monitor inflamrnation.
Inthe 7th chapterwe describe effects and side-effects of treatment with a recently
developed inhaled corticosteroid, fluticasone propionate (FP), in 35 children with
stable, moderate asthma, in a double blind placebo-controlled trial. After the
treatment period there was a follow-up period of 4 weeks during which only
bronchodilators were allowed. At home symptoms of asthma, the use of Br-
mimetics and peak expiratory flow (PEFR) were registrated in a diary twice daily.
Each month, lung function, bronchial hyperresponsiveness (PCrn-histamine) and
reversibility to Br-mimetics were detennined. We found that during treatrnent
wheezing decreased and all PEFR values increased in the FP group. FEV,
increased, PCro-histamine and reversibility decreased in the FP group. All the
observed changes were significant, with exception of the change in nocturnal
PEFR. The effect of FP on symptoms and lung function were transient, since
t47
Chapter 9
four weeks after cessation of FP, all parameters had returned to pre-treatrnent
values. Side-effects regarding influence of FP on the hypothalamus-pituitary-
adrenal axis (HPA-axis) were measured as serum and urinary cortisol concen-
tration under fasting conditions. During treatment serum cortisol did not change
and urinary cortisol significantly decreased in the FP group' only when the de-
crease was compared with anunexplained increase in the placebo group. we con-
clude that FP 100 pg bd is effective in children with moderate stable asthma' With
respect to side effects, additional studies are necessary to exclude suppression
of the HPA-axis during treatrnent with FP 100'pg bd'
Inthe 8rh chapterwediscuss the contribution of the studies presented in this thesis
to the pathophysiology of asthma and possible issues for future research, emerging
from this thesis.
r48


Proceedings - University of Groningen

   University of GroningenEosinophils in childhood asthmaHoekstra, Maarten OttoIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1996Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Hoekstra, M. O. (1996). Eosinophils in childhood asthma. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 09-09-2023Stellingen behorende bij het proefschrift van Maarten Otto Hoekstra Eosinophils in childhood asthma 1. 'Priming' van eosinofiele leucocyten kan ge'induceerd worden door het scheiden van erythrocyten en leucocyten in vitro met behulp van dextran. (Dit proefschrift) 2. Eosinofiele granulocyten van kinderen met een stabiel, matig ernstig astma zijn, gezien hun !age dichtheid, 'geprimed' in vivo. (Dit proefschrift) 3. De samenstelling van interleukines in het supernatant van kweken van gestimuleerde mononucleaire cellen van kinderen met astma suggereert het bestaan van een dysfunctie van de T-helper-1-cellen. (Dit proefschrift) 4. Het gebruik van de bepaling van serum ECP bij de monitoring van kinderen met astma, is onvoldoende door wetenschappelijk onderzoek onderbouwd. 5. De niet-invasieve bepaling van EON in de urine voor de monitoring van astma bij kinderen dient verder te worden onderzocht. (Dit proefschrift) 6. Voordat gesteld kan worden dat fluticasone propionaat bij kinderen met astma minder kans geeft op bijwerkingen dan de bestaande inhalatiecorticostero'iden, dient de 'pulmonale resorptie' van dit medicament eerst verder te worden onderzocht. 7. Het tijdrovend werk van het maken van een differentiaal diagnose blijkt in de praktijk een tijdsbesparende investering. 8. Specialistische laboratorium diagnostiek is alleen zinvol als de a priori kans op de te testen aandoening groot is. 9. In ervaren handen heeft het verrichten van flexibele bronchoscopie bij kinderen door een kinderarts in samenwerking met een anaesthesist een verwaarloosbaar complicatierisico. 10. Hoewel de grootste problemen van veel dokters tijdproblemen en geen geld­problemen zijn, wordt veelvuldig de indruk gewekt, dat het net andersom is. 11. De mening dat een goede assistent een dokter is, die ook na de werktijd nog in het ziekenhuis aanwezig is, dient kritisch te worden beschouwd. 12. Het probleem van het overbelaste wegennet in Nederland kan slechts worden opgelost, indien de kosten van het autorijden fors verhoogd worden. 13. Het principe van 'loon naar prestatie', dat menigeen aanspreekt, is in de praktijk nauwelijks uitvoerbaar, daar verschillende prestaties moeilijk te vergelijken zijn. 

Dissertations of the University of Groningen

   University of GroningenEosinophils in childhood asthmaHoekstra, Maarten OttoIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1996Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Hoekstra, M. O. (1996). Eosinophils in childhood asthma. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 14-02-2023Stellingen behorende bij het proefschrift van Maarten Otto Hoekstra Eosinophils in childhood asthma 1. 'Priming' van eosinofiele leucocyten kan ge'induceerd worden door het scheiden van erythrocyten en leucocyten in vitro met behulp van dextran. (Dit proefschrift) 2. Eosinofiele granulocyten van kinderen met een stabiel, matig ernstig astma zijn, gezien hun !age dichtheid, 'geprimed' in vivo. (Dit proefschrift) 3. De samenstelling van interleukines in het supernatant van kweken van gestimuleerde mononucleaire cellen van kinderen met astma suggereert het bestaan van een dysfunctie van de T-helper-1-cellen. (Dit proefschrift) 4. Het gebruik van de bepaling van serum ECP bij de monitoring van kinderen met astma, is onvoldoende door wetenschappelijk onderzoek onderbouwd. 5. De niet-invasieve bepaling van EON in de urine voor de monitoring van astma bij kinderen dient verder te worden onderzocht. (Dit proefschrift) 6. Voordat gesteld kan worden dat fluticasone propionaat bij kinderen met astma minder kans geeft op bijwerkingen dan de bestaande inhalatiecorticostero'iden, dient de 'pulmonale resorptie' van dit medicament eerst verder te worden onderzocht. 7. Het tijdrovend werk van het maken van een differentiaal diagnose blijkt in de praktijk een tijdsbesparende investering. 8. Specialistische laboratorium diagnostiek is alleen zinvol als de a priori kans op de te testen aandoening groot is. 9. In ervaren handen heeft het verrichten van flexibele bronchoscopie bij kinderen door een kinderarts in samenwerking met een anaesthesist een verwaarloosbaar complicatierisico. 10. Hoewel de grootste problemen van veel dokters tijdproblemen en geen geld­problemen zijn, wordt veelvuldig de indruk gewekt, dat het net andersom is. 11. De mening dat een goede assistent een dokter is, die ook na de werktijd nog in het ziekenhuis aanwezig is, dient kritisch te worden beschouwd. 12. Het probleem van het overbelaste wegennet in Nederland kan slechts worden opgelost, indien de kosten van het autorijden fors verhoogd worden. 13. Het principe van 'loon naar prestatie', dat menigeen aanspreekt, is in de praktijk nauwelijks uitvoerbaar, daar verschillende prestaties moeilijk te vergelijken zijn. 

University of Groningen Digital Archive

   University of GroningenEosinophils in childhood asthmaHoekstra, Maarten OttoIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1996Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Hoekstra, M. O. (1996). Eosinophils in childhood asthma. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 29-10-2022Stellingen behorende bij het proefschrift van Maarten Otto Hoekstra Eosinophils in childhood asthma 1. 'Priming' van eosinofiele leucocyten kan ge'induceerd worden door het scheiden van erythrocyten en leucocyten in vitro met behulp van dextran. (Dit proefschrift) 2. Eosinofiele granulocyten van kinderen met een stabiel, matig ernstig astma zijn, gezien hun !age dichtheid, 'geprimed' in vivo. (Dit proefschrift) 3. De samenstelling van interleukines in het supernatant van kweken van gestimuleerde mononucleaire cellen van kinderen met astma suggereert het bestaan van een dysfunctie van de T-helper-1-cellen. (Dit proefschrift) 4. Het gebruik van de bepaling van serum ECP bij de monitoring van kinderen met astma, is onvoldoende door wetenschappelijk onderzoek onderbouwd. 5. De niet-invasieve bepaling van EON in de urine voor de monitoring van astma bij kinderen dient verder te worden onderzocht. (Dit proefschrift) 6. Voordat gesteld kan worden dat fluticasone propionaat bij kinderen met astma minder kans geeft op bijwerkingen dan de bestaande inhalatiecorticostero'iden, dient de 'pulmonale resorptie' van dit medicament eerst verder te worden onderzocht. 7. Het tijdrovend werk van het maken van een differentiaal diagnose blijkt in de praktijk een tijdsbesparende investering. 8. Specialistische laboratorium diagnostiek is alleen zinvol als de a priori kans op de te testen aandoening groot is. 9. In ervaren handen heeft het verrichten van flexibele bronchoscopie bij kinderen door een kinderarts in samenwerking met een anaesthesist een verwaarloosbaar complicatierisico. 10. Hoewel de grootste problemen van veel dokters tijdproblemen en geen geld­problemen zijn, wordt veelvuldig de indruk gewekt, dat het net andersom is. 11. De mening dat een goede assistent een dokter is, die ook na de werktijd nog in het ziekenhuis aanwezig is, dient kritisch te worden beschouwd. 12. Het probleem van het overbelaste wegennet in Nederland kan slechts worden opgelost, indien de kosten van het autorijden fors verhoogd worden. 13. Het principe van 'loon naar prestatie', dat menigeen aanspreekt, is in de praktijk nauwelijks uitvoerbaar, daar verschillende prestaties moeilijk te vergelijken zijn. 

   University of GroningenEosinophils in childhood asthmaHoekstra, Maarten OttoIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1996Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Hoekstra, M. O. (1996). Eosinophils in childhood asthma. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 30-10-2023Stellingen behorende bij het proefschrift van Maarten Otto Hoekstra Eosinophils in childhood asthma 1. 'Priming' van eosinofiele leucocyten kan ge'induceerd worden door het scheiden van erythrocyten en leucocyten in vitro met behulp van dextran. (Dit proefschrift) 2. Eosinofiele granulocyten van kinderen met een stabiel, matig ernstig astma zijn, gezien hun !age dichtheid, 'geprimed' in vivo. (Dit proefschrift) 3. De samenstelling van interleukines in het supernatant van kweken van gestimuleerde mononucleaire cellen van kinderen met astma suggereert het bestaan van een dysfunctie van de T-helper-1-cellen. (Dit proefschrift) 4. Het gebruik van de bepaling van serum ECP bij de monitoring van kinderen met astma, is onvoldoende door wetenschappelijk onderzoek onderbouwd. 5. De niet-invasieve bepaling van EON in de urine voor de monitoring van astma bij kinderen dient verder te worden onderzocht. (Dit proefschrift) 6. Voordat gesteld kan worden dat fluticasone propionaat bij kinderen met astma minder kans geeft op bijwerkingen dan de bestaande inhalatiecorticostero'iden, dient de 'pulmonale resorptie' van dit medicament eerst verder te worden onderzocht. 7. Het tijdrovend werk van het maken van een differentiaal diagnose blijkt in de praktijk een tijdsbesparende investering. 8. Specialistische laboratorium diagnostiek is alleen zinvol als de a priori kans op de te testen aandoening groot is. 9. In ervaren handen heeft het verrichten van flexibele bronchoscopie bij kinderen door een kinderarts in samenwerking met een anaesthesist een verwaarloosbaar complicatierisico. 10. Hoewel de grootste problemen van veel dokters tijdproblemen en geen geld­problemen zijn, wordt veelvuldig de indruk gewekt, dat het net andersom is. 11. De mening dat een goede assistent een dokter is, die ook na de werktijd nog in het ziekenhuis aanwezig is, dient kritisch te worden beschouwd. 12. Het probleem van het overbelaste wegennet in Nederland kan slechts worden opgelost, indien de kosten van het autorijden fors verhoogd worden. 13. Het principe van 'loon naar prestatie', dat menigeen aanspreekt, is in de praktijk nauwelijks uitvoerbaar, daar verschillende prestaties moeilijk te vergelijken zijn. 

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