Pulmonary function after mechanical ventilation for respiratory syncytial virus induced respiratory failure in infancy

It is well established that the maximal level of pulmonary function reached
after puberty is a crucial determinant of the risk for chronic obstructive
pulmonary disease (COPD) in later life. COPD is defined by an FEV1/FVC ratio of
less than 70%, and thus subjects who start adult life with lower ratios will
attain this threshold much earlier. This irrefutably implies that any injury to
the developing paediatric lung will have a negative effect. Respiratory
syncytial virus (RSV) is the predominant pathogen of lower respiratory tract
disease (LRTD) in infants that can only be supportively managed. A significant
proportion of young infants hospitalised with RSV LRTD need to be mechanically
ventilated. Although life-saving for these infants, mechanical ventilation also
aggravates pre-existing lung injury yielding additional detrimental effects on
patients outcome (double-hit principle). Therapeutic modalities such
anti-inflammatory drugs (for instance corticosteroids) lack any benefit. This
is mainly due to the fact that the underlying pathophysiological mechanisms are
far from elucidated. This research project therefore is designed to study the
effects of RSV LRTD in mechanically ventilated infants on pulmonary function
during follow-up, as well as potential underlying pathophysiological mechanisms
so that ultimately therapeutic modalities can be developed that prevent a
decrease in lung function.

Primary Objective:
*To study differences in pulmonary function (i.e. increased airway resistance)
one year after hospitalisation for RSV LRTD between mechanically ventilated and
non-ventilated infants

Secondary Objectives:
*To study pathophysiological mechanisms contributing to impaired pulmonary
function (i.e. increased airway resistance) including clinical, virological and
immunological characteristics, level and time course of mechanical ventilation,
and presence of lung injury as defined by circulating biomarkers
*To study the difference in frequency of recurrent wheezing during the first
year following hospitalisation for RSV LRTD between mechanically ventilated and
non-ventilated infants
*To study the frequency of recurrent wheezing in relation to impaired pulmonary
function (i.e. increased airway resistance)

This is a prospective, longitudinal cohort-study of patients admitted with RSV
lower respiratory tract infection to the Beatrix Children*s Hospital/University
Medical Center Groningen comprising four consecutive RSV seasons (October to
March) between October 1, 2011 and March 31, 2015.

Not applicable

Measurements will be performed in all infants on day 1, 3 and 5 of admission
including blood sampling (2 ml per sampling) through a venous puncture in
non-ventilated infants or using the indwelling arterial line in ventilated
infants, nasopharyngeal aspirates in all infants and broncho-alveolar lavage
fluids in ventilated infants. Regional lung filling characteristics will be
measured using electrical impedance tomography (EIT). During the first year of
follow-up parents or legal care-takers of all included infants are asked to
daily fill out a patient diary, recording respiratory symptoms including cough,
rhinitis, wheezing, and consultation of a physician and use of bronchodilators.
One year after discharge, lung function testing including FRC and airway
resistance will be performed with the whole-body plethysmography in all
included infants. The risks associated with this project are considered
moderate: ventilated infants who undergo a broncho-alveolar lavage may
experience a brief period of a decrease in transcutaneously measured oxygen
saturation. Obtaining a nasopharyngeal aspirate in infants does not cause any
extra risk, but may be experienced as uncomfortable for a brief period in
non-ventilated infants. Blood sampling is done using the indwelling arterial
catheter in ventilated infants; however in non-ventilated infants a venous
puncture has to be performed. Lung function testing one year after discharge
requires the infant to be mildly sedated using oral chloralhydrate that is very
often used for procedural sedation in children; nevertheless, because of this a
physician trained in advanced paediatric life support will be present during
this procedure.