MONITOR CF: Monocytes In TiMaSCAN for monitoring respiratory infections in Cystic Fibrosis

In cystic fibrosis (CF), fast and effective treatment of acute lung attacks,
so-called pulmonary exacerbations, is important to limit deterioration and
damage to the lungs. These acute lung attacks are caused by infections.
Antibiotics are given as treatment, the choice being based on results of
previous airway cultures and empirically on previous good response. Bacteria
are identified by culture of sputum or swabs of the upper airways. However,
these methods are a) insensitive, since bacteria residing deep in the lungs are
not always present in the sputum; b) insufficiently specific, as asymptomatic
colonization in the upper respiratory tract may occur. To obtain more accurate
information, bronchoalveolar lavage fluid (BALF) can be used for culture.
However, BAL by bronchoscopy is an invasive procedure which must be done under
anesthesia in children and therefore cannot be obtained often. The current
treatment of pulmonary exacerbations is therefore based on symptoms and
suboptimal knowledge about the microorganisms that play a role at that specific
moment. Treatment of a lung attack can be improved if an accurate and rapid
assessment of a specific infection can be made before antibiotics are
administered.

We have developed a new diagnostic method called TiMaSCAN that can distinguish
infection in the lungs from colonization of the upper airways. TiMaSCAN is
based on the scanning of monocyte content in peripheral blood using flow
cytometry and pathogen-specific antibodies.
The optimal duration of antibiotic treatment for pulmonary exacerbations is a
matter of debate. The duration of an IV course is determined by improved lung
function and symptoms. In young children, however, lung function assessment is
difficult, requiring clinicians to rely on symptoms to guide treatment success,
which may not be accurate enough. Thus, there is an urgent need for a quick,
easy-to-perform test that is specific for CF bacteria and can measure whether
the treatment is effective.

Our hypothesis is that TiMaSCAN results will correlate with airway cultures and
that the amount of pathogen-positive TiMas will decrease over the course of
antibiotic treatment.

Our main aim is to validate the TiMaSCAN as both a diagnostic and monitoring
tool in the treatment of pulmonary exacerbations in CF patients.

Observational study, ex-vivo analysis of peripheral blood monocytes from
children with CF, correlations with results from airway cultures and clinical
data such as respiratory symptoms and spirometry.

In most patients a minor burden is associated with this study, with no
additional risks or benefits. No additional study visits are required. For this
study we plan to collect peripheral blood and sputum. The blood sample is taken
from the i.v. canula or central line at the time of insertion, during
treatment, and immediately after the course of antibiotics, just before it is
removed. Usually no additional puncture is required. Obtaining an extra tube of
blood does not place an additional burden on the patient.
Sputum is collected at the same time points as peripheral blood. If no sputum
can be coughed up, we will collect a cough swab. This method is also widely
used in routine care and does not pose a risk to the patient.
If a bronchoscopy with BAL is performed at the start of treatment, these
cultures will also be included in analysis. However, no bronchoscopy is
performed for research purposes only. Rest material is used for research
purposes.
Lung function is analysed by standard spirometry according to routine care