Multiple breath washout ter beoordeling van longfunctie bij kinderen met congenitale hernia diafragmatica

Kinderen met een congenitale hernia diafragmatica (CHD) kunnen geboren worden
met acute en ernstige longproblemen. Kinderen met deze longproblemen moeten met
een kunstmatige beademing en medisch ingrepen krijgen. De longfunctie van de
kinderen die deze cruciale periode overleven zal met de jaren naar bijna
normaal herstellen. Helaas blijven longklachten echter ook op oudere leeftijd
vaak aanwezig. Daarom worden kinderen met CHD regelmatig bij een kinderlongarts
gezien. Bij deze controles wordt de longfunctie doorgaans gemeten met
spirometrie (blaastest) en de bodybox. Deze metingen zijn vooral nuttig om de
longvolumes te meten. De longvolumes bij kinderen met CHD zijn rond de
puberteit echter veelal (laag)normaal. Er bestaat dan een verschil tussen de
uitkomsten van de longfunctietesten en de klachten die de patiënten ervaren.
De afgelopen jaren is er veel interesse gekomen voor een nieuwe longfunctietest
genaamd Multiple Breath Washout (MBW). MBW geeft een indicatie van schade aan
de kleine luchtwegen. Terwijl spirometrie en de body-box met name iets zeggen
over longvolumes en de doorgankelijkheid van de grote luchtwegen. In veel
longziektes zijn de problemen juist gesitueerd in de kleine luchtwegen, terwijl
de grote luchtwegen pas bij meer gevorderde longproblemen zijn aangedaan. Ook
bij CHD weten we dat schade aan en onderontwikkeling van de kleine luchtwegen
een rol in de klachten van de patiënten spelen, maar in welke mate is niet
precies bekend. MBW zou hier meer informatie over kunnen geven dan spirometrie
of de body-box, doch daar is nog geen onderzoek naar gedaan.
Met dit cross-sectionele onderzoek willen we MBW-metingen uit gaan voeren in 32
kinderen met een leeftijd van 5 tot 18 jaar. Patiënten zullen gevraagd worden
om een extra MBW test uit te voeren bij hun volgende controle bezoek, waarbij
spirometrie en body-box metingen al onderdeel zijn van de standaard follow-up
diagnostiek bij patiënten met CHD. De MBW-uitkomsten zullen vervolgens
vergeleken worden met de uitkomsten van de standaard longfunctietesten. Verder
zullen verbanden tussen MBW-uitkomsten en leeftijd, en de aanwezigheid van
prognostische factoren van de hernia aanwezig bij de geboorte verder onderzocht
worden. Het MBW-onderzoek, dat veilig en niet-invasief is, wordt extra verricht
bovenop de normale zorg/diagnostiek. De belasting zal derhalve erg laag zijn.

Our research project aims to answer 3 key questions:

1. How do MBW, spirometry and body-plethysmography outcomes compare in
survivors of CDH?

2. What is the relation between MBW outcomes in survivors of CDH and age?

3. Are prognostic factors of the herniation present at birth (e.g. location of
herniation, lung-to-head ratio, liver herniation) associated with increased
(i.e. worse) MBW outcomes in survivors of CDH?

Patients with a history of CDH regularly visit the hospital for follow-up with,
amongst others, their pediatric pulmonologist and surgeon. Patients with a
history of Bochdalek-type CDH and/or their parents will receive a call from
either their treating pediatric pulmonologist or surgeon. During this call,
they will be asked whether they are interested in receiving the patient
information file (PIF) of this study by mail. When patients and/or their
parents agree to participate in this study, the participation forms will be
signed at the next follow-up visit together with their treating pediatric
pulmonologist or surgeon. Patients with a hernia-type other than Bochdalek, or
patients who had any pulmonary surgery other than sequestration removal will
not be asked to participate. Furthermore, children with a pulmonary infection
requiring antibiotics within 4 weeks from the follow-up visit, or with a
pulmonary infection not requiring antibiotics within 2 weeks from the follow-up
visit are excluded from this study.
Only a MBW test will be scheduled in addition to the spirometry and
body-plethysmography tests which are part of routine care. During the MBW test
patients will be accompanied by a post-graduate medical student who has been
trained and certified in performing MBW tests with children of the target age
group. Before starting the test, the researcher will introduce and explain the
procedure to the patient and parents. The researcher will also ask the patient
to choose a program to watch on TV. Watching TV during the test helps to
distract the children which stimulates a tidal breathing pattern. Maintaining a
stable tidal breathing pattern is important for achieving a test result of good
quality.
When the test starts the patient will breathe through a snorkel-like mouthpiece
and wear a nose-clip. Therefore, a closed breathing circuit is created in which
only 100% oxygen is delivered to the patient. By inhaling only oxygen, the
subject will washout the resident nitrogen present in the lungs breath by
breath until the target concentration of 1/40th (2.5%) of the starting nitrogen
concentration has been reached. It is expected that in this population reaching
the target concentration will take approximately 2-3 minutes. However,
depending on the extent of peripheral airway damage this estimation could be
increased. After reaching the target concentration, the researcher will stop
the test which thereby completes one MBW trial. The patient can now remove his
mouth from the mouthpiece and breathe normal room air. After every trial there
is a waiting period of 1.5 times the trial time in order to wash the nitrogen
present in room air back into the lungs. After this waiting period, another
trial is started.
In order to successfully complete the MBW test occasion, at least two trials
will have to be of good quality. Factors which can decrease the quality of
trials are the opening of the closed circuit by a leak or unstable breathing
patterns of the child. the researcher will try to prevent problems in
acceptability by coaching and comforting the child to breathe calmly and to
stimulate the patient to focus on watching TV. One test occasion typically
includes several MBW-trials to obtain at least two trials that are technically
valid. The researcher will try to collect three successful trials, minimizing
the chance of losing the test occasion when one of the trials still turns out
to be unacceptable after post-test quality control. Dependent on the amount of
trials needed to achieve three or more acceptable trials and the amount of
peripheral airway damage present, total testing time will usually take 30 to 45
minutes including the introduction and explanation of the test to patient and
parents. A maximum of two subjects per age-group will be replaced when subjects
do not succeed in achieving two technically valid MBW-trials. MBW-test success
rates will be reported in our study and will be compared to spirometry and
body-box success rates.
In this study we will furthermore ask the patients and parents for permission
to use the spirometry and body-plethysmography outcomes from the same follow-up
visit for our study. These outcomes will be needed to answer our research
questions. Furthermore, we will ask permission to use demographic data of the
patients, and prognostic factors of the herniation present at birth. The
prognostic factors will include the side of the herniation in the diaphragm,
the lung-to-head ratio, the presence of liver herniation, the requirement of
extracorporeal membrane oxygenation (ECMO) and whether the child was born
prematurely including the gestational age at birth. These data will all be
collected either during a regular follow-up visit, or retrospectively from the
electronic patient file by a member of the research team. Collection of these
data will therefore not pose any extra burden on the patient and his/her
parents.

zeer geringe belasting, geen risico's