Children with absent surfactant protein D in bronchoalveolar lavage have more frequently pneumonia

Abstract

Surfactant protein D (SP-D) is an important component of the pulmonary host defense system. We hypothesized that bronchoalveolar lavage (BAL) SP-D levels are lower in children presenting with recurrent bronchitis, providing evidence for a role of SP-D in human respiratory diseases. SP-D levels in BAL were measured in 45 children, who suffered from recurrent bronchitis for an average of 2-3 yr. Clinical outcome was assessed 2 yr after BAL. For comparison, BAL fluids from 15 control children without respiratory symptoms were evaluated. Among the 45 children with recurrent bronchitis, 12 had no SP-D in their BAL at the time of investigation. These SP-D-deficient patients had more frequently pneumonias and their long-term outcome was worse than that of the children with detectable SP-D. No genetic cause could be identified for the SP-D deficiency. Among the children with recurrent bronchitis and SP-D clearly detectable in BAL, those with the diagnosis of allergic asthma had threefold elevated levels compared with controls. In accordance with animal and in vitro data, elevated SP-D concentrations in BAL may represent an up-regulation due to allergic airway inflammation. In contrast, SP-D deficiency due to consumption or failure to up-regulate SP-D may be linked to pulmonary morbidity in children.

Heterogeneous Pulmonary Phenotypes Associated With Mutations in the Thyroid Transcription Factor Gene NKX2-1

“…Children with severe RSV infection or recurrent pneumonias may have decreased or absent levels of SP-D in BAL fl uid during the acute phase of the infection, such that the role of NKX2-1 in SP-D gene expression is less clear. 27,28 Murine SP-D gene expression, as assessed by microarray, was actually increased in transgenic mice expressing a phosphorylation mutant form of Nkx2-1 , suggesting negative regulation by TTF-1; however, no changes in human SP-D gene expression were detected with either gain or loss of function approaches in vitro. 19,29 Thus, it is diffi cult to determine the relationship between the NKX2-1 mutations, SP-D expression, and the recurrent infections in these children, especially in light of other children in this report with NKX2-1 mutations and recurrent infections but who do not have evidence of decreased SP-D expression.…”

Can immunogenetics illuminate the diverse manifestations of respiratory infections?

“…Low levels of pulmonary surfactant proteins are associated with increased risk of pneumonia [Griese et al 2008]. A polymorphism in surfactant protein B, SP-B þ1580 (T/C) was associated with increased risk of pneumonia in one cohort study [Quasney et al 2004], but no further studies have been reported.…”

Key mediators in the immunopathogenesis of allergic asthma

“…In human patients, SP-D inhibited the chemotaxis of eosinophils suggesting an anti-inflammatory role in the lungs of asthmatic subjects (82). Children with decreased or absent SP-D in bronchoalveolar lavage fluid were found to have more frequent respiratory diseases (83). Most of the data seem to suggest that both human and murine SP-A/D seem to play a role in controlling allergy and airway inflammation.…”