Ventilator induced lung injury by mechanical ventilation in children with respiratory syncytial virus infection.

Respiratory Syncytial Virus (RSV) lower respiratory tract infection (LRTI) is
the most frequent cause of Pediatric Intensive Care Unit (PICU) admission for
mechanical ventilatory support in infants during the winter season. Life-saving
mechanical ventilation (MV) however may induce or aggravate pulmonary
inflammation and lung injury. When pulmonary inflammation is already present
when MV is applied, this inflammation is probably enhanced. Therefore, it is
reasonable to assume that MV will profoundly modulate RSV induced inflammation.
Currently, the role of ventilation-induced lung injury (VILI) is studied by the
applicants in a mouse model. The aim of the proposed study is to translate the
same hypothesis to humans: mechanical ventilation aggravates RSV-induced airway
inflammation.

The aim of this study is to compare the time course of cytokines (markers for
inflammation) in the following 3 groups: RSV-positive, ventilated patients;
RSV-positive, non-ventilated patients and RSV-negative, ventilated patients.
The main hypothesis is that MV aggravates RSV-induced airway inflammation as
determined by repeated measurement of local cytokine concentrations.

The pilot study will be an observational multi-center, prospective, case
control study.

From each patient a maximum of 4 samples [aspirates] will be obtained.
Burden:
* Nasopharyngeal aspiration is a non-invasive technique where mucus is
suctioned from the nose. The burden for the patient is low, consisting of
discomfort during less than 10 seconds. Most children admitted to the hospital
for respiratory illness during the winter season undergo this diagnostic
procedure to determine if they are RSV positive or negative. Also due to
obstruction of the nose by mucus the nose will be suctioned frequently in LRTI
patients. Medical staff is experienced with this technique. No complications
have been described.
* Endotracheal aspiration is a non-invasive technique where mucus is suctioned
from the endotracheal tube. The burden for the patient is low and all children
requiring mechanical ventilation, regardless of the reason for their
respiratory insufficiency, undergo this procedure routinely several times per
day to prevent endotracheal tube obstruction and subsequent ventilator
problems. Endotracheal suctioning is also used for several diagnostic
procedures and poses little risk. No complications have been described.
* Bloodsampling: Every 48 hours 2 ml blood is taken from a central venous,
arterial catheter or during peripheral venous cannulation during anesthesia for
cellular immunological studies. This amount has been considered safe by the
WKZ/UMCU METC in our previous studies in a population with identical inclusion
criteria.

Possible benefit:
There is no clear clinical benefit for the infants participating in this
proposed study.
* Nasopharyngeal aspiration: the sample before intubation is necessary to clear
the upper airways (infants obligatory breathe through the nose). Subsequent NPA
samples have no possible benefit.
* Endotracheal aspiration: preventing tube obstruction and therefore avoiding
ventilator problems.