Introduction
Trisomy 21 or Down syndrome (DS) is a relatively common human genetic
disorder. It is well known for the characteristic dysmorphic features,
cognitive impairment and hypotonia, but patients also have a high
incidence of congenital anomalies in several organ systems: most
frequently affected are the heart, gastrointestinal tract and
respiratory system . These features makes them more prone to airway
obstruction and other respiratory problems . Children with DS are more
vulnerable for infections, probably multifactorial in origin but an
altered immune status has also been described. Studies show that
respiratory problems such as upper and lower respiratory tract
infections (e.g. otitis media, tonsillitis, pneumonia, bronchiolitis)
are the most common admission diagnoses in this patient population.
In a previous study, we focused on the anatomy of the lower airways and
reviewed endoscopic results to compare the prevalence of airway
anomalies in a population of children with DS with a control group (both
with chronic or recurrent respiratory symptoms). In conclusion, we found
a significantly higher prevalence of both isolated and combined airway
malformations compared to controls (with the occurrence of one or more
anomalies in 71% of endoscopies in DS versus 32% of controls, p
<0.001). This confirmed the conclusions of previous
small-scale studies . However, little is known about the microbiota of
these children.
In the past, the lungs were thought to be a sterile environment. We now
know that the lower airways are a complex ecosystem, with a rich mucosal
flora that differs from the microbiome in the upper airways (which in
turn shows major differences in microbiome when comparing for example
the nasal and oral cavity). However, examining the lower airway
microbiota is challenging. This is because of the technical difficulties
in accurate sampling and also the extremely low bacterial burden in
healthy lungs. While the upper respiratory tract has a high bacterial
burden due to continuous exposure via ingestion and inhalation, this is
100 to 10.000 times lower in the lower airways. Although the vocal cords
act as a barrier, there are still continuous bacterial challenges due to
microaspiration, postnasal drip, regurgitation, hematogenous spread and
inhalation. In addition to these exposures, use of antibiotics or
steroids, coinfection with viruses and availability of nutrients can
play important roles in the shaping of a specific microbiome and
immunological fenotypes .
Studies in children with chronic cough and diagnosis of protracted
bacterial bronchitis, have shown clinically significant levels of the
following microorganisms in BAL (bronchoalveolar lavage) fluid:
Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis
and Staphylococcus aureus. These pathogens were associated with altered
bacterial community structure (lower alpha diversity of the respiratory
microbiota), higher bacterial biomass and higher inflammatory parameters
such as neutrophil percentage and several interleukins, compared to
controls .
A few case reports from the 1980-1990’s exist that describe atypically
severe lower airway infections in children with DS. Cant et al described
a series of 4 DS patients presenting with acute bacterial tracheitis.
Three of them had cultures positive for H. influenzae and one remained
sterile, probably due to sampling done after several doses of antibiotic
therapy. All of them were severely ill and required mechanical
ventilation. Orlicek et al described another series of 3 young DS
patients with severe bilateral pneumonia with Mycoplasma pneumonia as
causative agent. A report by Winters et al described a case of lethal
pneumonia in a DS patient caused by Bordetella bronchiseptica, which is
a microorganism generally found in animal species but in rare cases also
causes severe infections in immunocompromised patients. These reports
suggest a susceptibility in DS patients for atypical microorganisms or
atypical course of infection. However, these reports are rare and
non-recent. Further data are lacking.
Therefore, the aim of this study is to compare microbiological data
(colonization) from the lower airways by endoscopic investigation in a
cohort of children with DS from our institution, to a group of controls
without significant medical history. This may deliver valuable
information for future decision-making in terms of treatment.