Inflammatory markers in Broncho-alveolar Lavage fluid as risk factors for Lung disease in infants with Cystic Fibrosis: the I-BALL study

Airway disease, featuring early and intense inflammation and leading to
progressive lung damage, is the main cause of morbidity and mortality in cystic
fibrosis (CF). Mechanisms of CF airway inflammation remain unclear, hampering
development of better treatments. Recent introduction of heel-prick screening
for CF provides a unique longitudinal cohort of CF infants, in which the early
phase of airway disease can be assessed. In our hospital we set up a clinical
protocol for monitoring these infants in a structured way, using chest computed
tomography (CT) and bronchoscopies with collection of broncho-alveolar lavage
fluid (BALF) to assess early lung damage. Our protocol is designed according to
the protocol used by the Australian AREST-CF consortium. Preliminary data from
Dr Scholte's group show that lipid profiles differ in BALF from CF infants with
a high score for lung damage, compared with a low score (minimal lung damage).
Some of these lipids are products of activated polymorphonuclear neutrophils
(PMN*s). Others are receptor-activating molecules involved in the resolution of
inflammation and tissue injury. Also, in a pilot study by Dr Tirouvanziam's
group, it was shown that CF airway PMNs are differently programmed than in
normal airways, which leads to increased release of inflammatory factors and
toxic enzymes. We hypothesize that CFTR deficiency causes abnormal inflammatory
signaling in the lung of CF infants, resulting in abnormal programming of
infiltrating PMNs, and subsequently excessive and chronic lung disease.

To better understand the progression of early CF lung disease we aim to study
lipid profiles and PMN dysfunction in relation to the severity of early lung
disease in infants with CF, using BALF samples and peripheral blood. To
optimally study these very precious samples, we will make use of
state-of-the-art technologies for in vivo profiling and in vitro testing of PMN
function, including lipidomics and innovative cell- and fluid-based tools.
Understanding the mechanisms at play in CF airway inflammation as it occurs in
infants may lead to new paths for early intervention

This is an observational, exploratory study aimed at lipid and PMN biomarker
evaluation in excess BALF samples from CF infants, the outcomes of which will
be correlated with clinical outcomes, primarily the presence of bronchiectasis
on chest CT

In most patients no additional burden, risks or benefits are associated with
this study. The material used will be leftover material (not used for clinical
studies) of BALF from patients that is collected in the context of the current
AREST-CF program. However, in some patients 1 or 2 extra aliquots of saline may
be necessary to obtain enough material. This adds a minimal additional burden
to the patients, with no extra risk. Also as standard procedure several blood
samples are taken during anaesthesia for routine investigations for the annual
check. During this blood sampling, an extra vial EDTA blood will be taken for
this study, and there will be no extra puncture for that.