Recovery after community acquired pneumonia in children: The short and long-term consequences

Respiratory tract infections (RTIs) are prevalent among children, with lower
respiratory tract infections (LRTIs), including pneumonia, bronchiolitis, and
wheezing illness, posing significant health risks. Pneumonia, in particular, is
a leading cause of morbidity and mortality in children under five years old,
with a rising incidence observed in older age groups over the past year.
Pneumonia is an infection of lung tissue caused by a combination of viruses and
bacteria.
In some children, pneumonia leads to hospital admission with antibiotic
treatment and oxygen support. When parents return with their child to the
outpatient clinic, they often report that their child still has long-term
symptoms, such as fatigue, reduced appetite or a change in behavior. Until now,
it is unknown how long these symptoms persist. We aim to study the possible
long-term symptoms of children who were admitted with community-acquired
pneumonia (CAP) using questionnaires and an accelerometer.

Furthermore, we want to study the association between the composition of the
microbiome, inflammatory responses and the duration of complete recovery as
well as the amount of recurrent lower respiratory tract infections.
Community-acquired pneumonia (CAP) has a polymicrobial etiology, involving
various viral and bacterial pathogens, primarily originating from the upper
respiratory tract or nasopharynx. During a pneumonia, the balance between the
bacteria in the airways (which is important for health) is disrupted: there are
few good bacteria and many pathogenic bacteria. It is not yet known whether
this disruption in the microbiome recovers, and whether it affects recovery
after pneumonia. For example, a sustained disruption of the microbiome could
increase the risk of new infections. In addition, antibiotics do not only harm
the pathogenic, but also the "good" bacteria, and little is known whether the
microbiome recovers after the use of antibiotics. Viruses also constitute part
of the nasopharyngeal microbiome, regardless of respiratory tract infection
presence and we want to study the role of viruses in recovery. Furthermore, the
gut microbiota contributes to RTI pathogenesis through the gut-lung axis,
modulating respiratory tract immunity.
Furthermore, the inflammatory milieu plays a crucial role in host
susceptibility to infection and post-infection sequelae. Recent advancements in
minimally invasive nasal sampling techniques allow for the detection of
inflammatory markers associated with specific microbiota species, offering
valuable insights into the pathogenesis of respiratory infections in children.
We expect to gain new insights into the pathogenesis of lower respiratory tract
infections. This could enable new preventive measures in future.

Additionally, we want to study whether pneumonia affects the heart function in
children. Cardiac complications are common in adults with CAP, like myocardial
dysfunction, new or worsening arrhythmias or myocardial infarction, with heart
failure occurring in about 14% of cases. Similar complications, including
myocarditis, are seen in children with COVID-19, often linked to severe
inflammatory states. However, limited data exist on cardiovascular involvement
in children without severe inflammation. The relationship between CAP and
cardiac function in children remains unclear, warranting further investigation.
Especially as heart function also affects recovery of the child and its future.

Primary objective:
- To study the impact of community acquired pneumonia in children on persistent
symptoms and quality of life, from admission in hospital until one year after
discharge.

Secondary objectives:
To investigate/assess:
- The association between demographic, clinical and microbial factors on still
having persistent symptoms, as defined by the parents, at 3 months.
- The association between demographic, clinical and microbial factors, on the
recurrence of CAP and other LRTI*s following hospital admission.
- The cardiac function (as addressed by echocardiography and biomarkers of
cardiac (dys)function) in children diagnosed with CAP during the acute illness
and the convalescent period.
- The composition of the respiratory and gut microbiome, in children diagnosed
with CAP, on admission, after 5-7 days and after 4-6 weeks.
- The nasal inflammatory profile, in children diagnosed with CAP, on admission,
after 5-7 days and after 4-6 weeks.
- The association between demographic, clinical and microbial factors on
persisting symptoms and Quality of Life (QoL), such as sleeping, appetite,
motor functioning, social functioning, problem behaviour, communication, and
positive and negative emotional functioning, in children after CAP infection
*

Observational prospective cohort study. The health status and recovery,
(defined as, the child*s health status returned to his/her normal state of
health as reported by parents), of children who are hospitalized with CAP will
be studied from admission until one year after discharge. If a recurrent
infection occurs, defined as a new occurrence of a clinical diagnosed lower
respiratory tract infection (LRTI), characterized by fever in combination with
increased breathing work and breathing frequency, occurs within the first year,
the follow-up period will be prolonged with one extra year with a maximum of 3
years.

Participation in this study holds no more risks than negligible risks. We
believe that the risk of this study is no more than negligible for the
participants since most sampling methods are non-invasive and generally
accepted as fully safe. Sampling moments will take place during
hospitalization, at home and on regular visits to the outpatient department.
There is no personal benefit for the child or the parents.
We will follow the code of conduct relating to expressions of objection by
minors participating in medical research, as stated by the CCMO.
The sampling moments including signing of the informed consent will take less
than 30 minutes of participant*s time. The echocardiographic examinations will
also take about 30 minutes and will be done twice (1x during admission and 1x
during a regular visit 4-6 weeks after discharge).