RATIONALE: The majority of previous studies investigating asthma genetics have focused on cohorts with stable disease and have not defined mechanisms important during acute asthma. CD14 and CC16 each play a key role in biologically important inflammatory pathways and the gene of each has a functional promoter-region polymorphism. OBJECTIVES: This study was designed to determine the influence of these polymorphisms on plasma levels of their products and clinical disease during acute asthma. We hypothesized that genotype-related differences in CD14 and CC16 production would be more marked during acute asthma and related to disease severity. METHODS: We studied 148 children on presentation with acute asthma and again in convalescence. CD14 C-159T and CC16 A38G genotypes were determined, and plasma levels of soluble CD14 (sCD14) and CC16 were measured at both times. MEASUREMENTS AND MAIN RESULTS: During acute asthma, plasma sCD14 levels were higher for the whole group (p = 0.003), but increases were only in subjects with CD14 -159TT (p = 0.003) and -159CT (p = 0.004), and not in those with -159CC. Plasma CC16 levels were also elevated acutely for the whole group (p = 0.013), but only in those with CC16 38GG (p = 0.043) and 38AG (p = 0.014), and not in those with CC16 38AA. Subjects with CD14 -159CC and CC16 38AA were more likely to have moderate or severe acute asthma. CONCLUSIONS: Plasma levels of sCD14 and CC16 were higher during acute asthma in the subjects. Those with CD14 -159CC and CC16 38AA had no change in sCD14 and CC16 levels and more severe asthma.
RATIONALE: The majority of previous studies investigating asthma genetics have focused on cohorts with stable disease and have not defined mechanisms important during acute asthma. CD14 and CC16 each play a key role in biologically important inflammatory pathways and the gene of each has a functional promoter-region polymorphism. OBJECTIVES: This study was designed to determine the influence of these polymorphisms on plasma levels of their products and clinical disease during acute asthma. We hypothesized that genotype-related differences in CD14 and CC16 production would be more marked during acute asthma and related to disease severity. METHODS: We studied 148 children on presentation with acute asthma and again in convalescence. CD14C-159T and CC16A38G genotypes were determined, and plasma levels of soluble CD14 (sCD14) and CC16 were measured at both times. MEASUREMENTS AND MAIN RESULTS: During acute asthma, plasma sCD14 levels were higher for the whole group (p = 0.003), but increases were only in subjects with CD14 -159TT (p = 0.003) and -159CT (p = 0.004), and not in those with -159CC. Plasma CC16 levels were also elevated acutely for the whole group (p = 0.013), but only in those with CC16 38GG (p = 0.043) and 38AG (p = 0.014), and not in those with CC16 38AA. Subjects with CD14 -159CC and CC16 38AA were more likely to have moderate or severe acute asthma. CONCLUSIONS: Plasma levels of sCD14 and CC16 were higher during acute asthma in the subjects. Those with CD14 -159CC and CC16 38AA had no change in sCD14 and CC16 levels and more severe asthma.
Authors: Desmond W Cox; Joelene Bizzintino; Giovanni Ferrari; Siew Kim Khoo; Guicheng Zhang; Siobhan Whelan; Wai Ming Lee; Yury A Bochkov; Gary C Geelhoed; Jack Goldblatt; James E Gern; Ingrid A Laing; Peter N Le Souëf Journal: Am J Respir Crit Care Med Date: 2013-12-01 Impact factor: 21.405
Authors: Sofie Halmø Hürdum; Guicheng Zhang; Siew-Kim Khoo; Joelene Bizzintino; Kimberley Marie Franks; Katie Lindsay; Anthony David Keil; Desmond William Cox; Jack Goldblatt; Yury Alexandrovich Bochkov; James Gern; Charlotte Suppli Ulrik; Peter Neils Le Souëf; Ingrid Alisa Laing Journal: Int J Pediatr Child Health Date: 2015-08
Authors: J Bizzintino; W-M Lee; I A Laing; F Vang; T Pappas; G Zhang; A C Martin; S-K Khoo; D W Cox; G C Geelhoed; P C McMinn; J Goldblatt; J E Gern; P N Le Souëf Journal: Eur Respir J Date: 2010-08-06 Impact factor: 16.671