Abstract
Chronic suppurative lung disease (CSLD) is characterized by the presence of a chronic wet or productive cough and recurrent lower respiratory infections. The aim of this study was to identify features of innate, cell-mediated and humoral immunity that may increase susceptibility to respiratory infections in children with CSLD. Because non-typeable Haemophilus influenzae (NTHi) is commonly isolated from the airways in CSLD, we examined immune responses to this organism in 80 age-stratified children with CSLD and compared their responses with 51 healthy control children. Cytokines involved in the generation and control of inflammation (IFN-γ, IL-13, IL-5, IL-10 at 72 hours and TNFα, IL-6, IL-10 at 24 hours) were measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. We also measured circulating IgG subclass antibodies (IgG1 and IgG4) to two H. influenzae outer membrane proteins, P4 and P6. The most notable finding was that PBMC from children with CSLD produced significantly less IFN-γ in response to NTHi than healthy control children whereas mitogen-induced IFN-γ production was similar in both groups. Overall there were minor differences in innate and humoral immune responses between CSLD and control children. This study demonstrates that children with chronic suppurative lung disease have an altered systemic cell-mediated immune response to NTHi in vitro. This deficient IFN-γ response may contribute to increased susceptibility to NTHi infections and the pathogenesis of CSLD in children.
Highlights
Bronchiectasis and chronic suppurative lung disease describe a syndrome of persistent or recurrent respiratory symptoms predominantly characterized by chronic productive or wet cough
We found that a high proportion of children in the Chronic suppurative lung disease (CSLD) group were identified by their parent as having Indigenous Australian ancestry, we have grouped children as either having known Indigenous Australian ancestry or with no, or unknown, Indigenous Australian ancestry
As CSLD was found to be prevalent in children of Indigenous descent, we investigated if this contributed to the differences in IFN-c observed between children with CSLD and healthy controls (HC) children
Summary
Bronchiectasis and chronic suppurative lung disease ( collectively termed CSLD) describe a syndrome of persistent or recurrent respiratory symptoms predominantly characterized by chronic productive or wet cough. Non-typeable Haemophilus influenzae (NTHi) are Gramnegative bacteria commonly associated with chronic upper and lower respiratory disease It is the dominant species isolated from the lower airways of children and adults with chronic respiratory symptoms [6,7,8]. Altered NTHi-specific cytokine responses, including Th2-skewed cytokine profiles have been reported in adults (.50 years of age) with established bronchiectasis or COPD and impaired lung function [11,13]. It is unclear whether these alterations were involved in disease induction, or rather arose as a consequence of systemic inflammation in adults with chronic, severe disease [14,15]. A study in children with milder disease of short duration may help elucidate some of these unresolved issues
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