Thesis defense Mischa Koenen

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Recurrent respiratory tract infections (rRTIs), common in young children, mainly result from viral infections that typically affect the respiratory mucosa. These infections can damage developing respiratory tissue, potentially leading to long-term complications like chronic obstructive pulmonary disease (COPD) and increased respiratory mortality in adulthood. Traditional diagnostics for rRTIs often focus on serum antibody levels to identify potential immune deficiencies, yet such deficiencies are identified in only a small fraction of affected children.
This thesis focuses on improving rRTI diagnostics by examining immune responses, specifically IgA levels, and respiratory microbiota in affected children. Findings reveal that IgA deficiency is more common in children with rRTIs and is linked to specific gut bacteria, notably Bifidobacterium, suggesting these bacteria could enhance mucosal immunity through the gut-lung axis.

Despite being used in the clinical diagnostic trajectory, serum antibody do not predict disease severity in children with rRTIs. However, measuring polyreactive salivary IgA, which binds broadly to pathogens, did prove predictive of rRTI severity in these children. Low polyreactive IgA levels in saliva were associated with higher viral load, more severe RTI symptoms, and increased Haemophilus influenzae on the respiratory tract.

In conclusion, while serum antibody levels help identify antibody deficiencies, they do not predict disease severity in children with rRTIs. Mucosal markers, such as polyreactive salivary IgA and H. influenzae abundance, show promise as diagnostic tools, potentially guiding targeted treatments, including probiotics or influenza vaccinations to enhance mucosal immunity in young children with rRTIs.