Respiratory syncytial virus (RSV) infection has been implicated in the pathogenesis of bronchial asthma. In both diseases, interleukin (IL)-4 and IL-13 play important roles. By investigating IL4 and IL13 polymorphisms in 131 children with severe RSV infection and 270 control subjects, we found an association between IL13 polymorphism -1112C/T and severe RSV infection (P = .026). Furthermore, certain haplotypes showed an even stronger association with severe RSV infection (P = .0008). The results suggest that there is a common genetic background in children with severe RSV infection and bronchial asthma. More studies are needed to clarify whether RSV infection provokes asthma or whether RSV infection occurs in children who are genetically predisposed to a pronounced T helper 2 immune response and subsequently develop bronchial asthma.

Respiratory syncytial virus (RSV) is the most common viral respiratory pathogen during infancy world wide. It induces innate and adaptive immune response in host cells. The toll like receptor 4 (TLR4)/CD14 complex is particularly important for the initiation of an innate immune response to RSV. Thus we were interested whether an association exists between severe RSV associated diseases and polymorphisms within TLR4 and CD14.We genotyped the CD14 promotor polymorphism -C159T and the two common TLR4 amino acid variants (D259G, and T359I) in 131 infants with severe RSV associated diseases and 270 controls. Statistical analyses of single polymorphisms made use of the Armitage’s trend test, haplotypes were calculated by FAMHAP, FASTEHPLUS and Arlequin.All polymorphisms were in Hardy Weinberg Equilibrium. We found marginal association between amino acid exchange D259G in TLR4 with RSV infection p = 0.0545). Furthermore, haplotypes analysis of the two TLR4 polymorphisms by three independent programs revealed association of haplotypes with severe RSV infection (p ≤ 0.0010). In contrast, the promotor polymorphism within CD14 was not associated with susceptibility to RSV disease. We conclude from our study, that TLR4 polymorphisms, and particularly the haplotypes, may influence the genetic predisposition to severe RSV infection.

Tumor necrosis factor (TNF-)alpha is a proinflammatory cytokine that is important in the innate host defence and thus in the defence of infectious agents. However, in excess it provokes the development of chronic inflammatory diseases. The aim of this study was to test association of TNF with severe RSV bronchiolitis as example of an infectious disease and asthma as representative for a chronic inflammatory condition. The following study populations were genotyped for 4 polymorphisms within TNF-beta (rs909253) and TNF-alpha (rs1799964, rs1799724, rs1800629): 322 asthmatic children, 151 children with severe respiratory syncytial virus (RSV) bronchiolitis and 270 controls. Furthermore, serum TNF-alpha levels were measured by a FlowCytomix Assay. Asthma showed association with two TNF-alpha polymorphisms as well as with TNF haplotypes (p = 0.0050). In contrast, RSV bronchiolitis was associated with TNF haplotypes (p < 0.00001) but not with any single polymorphism. In addition, TNF-alpha serum levels correlated with rs1799724 (p = 0.034). A genetically mediated up-regulation of TNF-alpha expression might provoke a pronounced inflammation of the airways and thus a more severe course of RSV infection as well as the onset of asthma. It remains to be elucidated whether severe RSV bronchiolitis starts TNF-alpha upregulation and is one first step in the direction to asthma later in life, or whether both diseases are independent from each other and supported by TNF-alpha upregulation.

BackgroundSurfactant proteins (SP) are important for the innate host defence and essential for a physiological lung function. Several linkage and association studies have investigated the genes coding for different surfactant proteins in the context of pulmonary diseases such as chronic obstructive pulmonary disease or respiratory distress syndrome of preterm infants. In this study we tested whether SP-B was in association with two further pulmonary diseases in children, i. e. severe infections caused by respiratory syncytial virus and bronchial asthma.MethodsWe chose to study five polymorphisms in SP-B: rs2077079 in the promoter region; rs1130866 leading to the amino acid exchange T131I; rs2040349 in intron 8; rs3024801 leading to L176F and rs3024809 resulting in R272H. Statistical analyses made use of the Armitage's trend test for single polymorphisms and FAMHAP and FASTEHPLUS for haplotype analyses.ResultsThe polymorphisms rs3024801 and rs3024809 were not present in our study populations. The three other polymorphisms were common and in tight linkage disequilibrium with each other. They did not show association with bronchial asthma or severe RSV infection in the analyses of single polymorphisms. However, haplotypes analyses revealed association of SP-B with severe RSV infection (p = 0.034).ConclusionThus our results indicate a possible involvement of SP-B in the genetic predisposition to severe RSV infections in the German population. In order to determine which of the three polymorphisms constituting the haplotypes is responsible for the association, further case control studies on large populations are necessary. Furthermore, functional analysis need to be conducted.

Background: Interleukin 8 (IL8) belongs to the family of chemokines. It mediates the activation and migration of neutrophils from peripheral blood into tissue and hereby plays a pivotal role in the initiation of inflammation. Thus it is important in inflammatory lung diseases like bronchial asthma or severe infections by Respiratory Syncytial Virus (RSV). IL8 acts through binding to the IL8-Receptor alpha (IL8RA). For both genes association with asthma has been described. In addition, IL8 has been found in association with RSV bronchiolitis. The aim of our study was to test both genes for association with asthma and severe RSV infections. In addition we were interested in whether a common genetic background of both diseases exists in regards to these genes.