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.