The authors concluded that the severity of AVB by RSV appears to be associated with constitutional and environmental factors. 53 One study analyzed 52 children with AVB by RSV (26 outpatients, 21 hospitalized in the hospital ward, and five admitted to the ICU), and found that the presence of Asp299Gly and Thr399Ile polymorphisms in the TLR4 gene, and a dysfunction of peripheral blood mononuclear cells stimulated by phytohemagglutinins expressed by hyper-responsiveness

in response to lipopolysaccharides, were associated with increased severity of AVB by RSV. 54 At the evaluation of D259G and T359I polymorphisms HER2 inhibitor of TLR4 in 131 infants with severe AVB by RSV compared with 270 MK-8776 in vitro controls, polymorphisms alone were not associated with disease severity, but the presence of a gene haplotype with both polymorphisms showed a significant association with severity (p < 0.001). 55 One study investigated whether polymorphisms in other TLRs, in addition to TLR4, could be related to susceptibility to AVB by RSV. Thus, 19 polymorphisms in TLRs 1, 2, 3, 5, 6, 9, and 10 were evaluated; an association was found between polymorphisms in receptors 9 and 10. 56 In the evaluation of 106 children hospitalized for AVB by RSV and 120 controls

(healthy adults with no history of severe respiratory infection) to verify the association of three polymorphisms (-28C/G, -403G/A, and In1.1T/C) in the RANTES gene with disease severity, there was no association

between disease severity and polymorphisms in isolation, but the combination of the three polymorphisms, forming a gene haplotype, was more common in cases than in controls, leading the authors to conclude that there was an association between polymorphisms in the RANTES gene and severity of AVB by RSV. 57 One study found that Thr1Meth polymorphism (rs10735810) in the vitamin D receptor was associated with AVB, with the T “minor” crotamiton allele showing a greater propensity to AVB.58 Another study analyzed 384 single nucleotide polymorphisms in 470 children hospitalized for AVB by RSV and 1,008 controls, and found that polymorphisms in the vitamin D receptor (rs10735810), JUN (rs11688), IFNA5 (rs10757212), and NOS-2 (rs1060826) genes showed association with AVB. The authors concluded that polymorphisms in innate immune response genes are important in determining susceptibility to the AVB. 59 Researchers evaluated whether the presence of polymorphisms in the CX3CR1 receptor present in leukocytes, which binds to G protein of RSV, could have a correlation with AVB severity. They evaluated 82 children hospitalized for AVB by RSV, comparing them with 120 adults with no history of severe respiratory infection, and concluded that the T280 M polymorphism was more frequent in cases than in controls (37.8% vs. 20.8%; OR: 2.03; 95% CI: 1.1 to 3.