IL-13 Gene Polymorphisms are Associated With Rhinosinusitis and Eosinophilic Inflammation in Aspirin Intolerant Asthma

PURPOSE: Aspirin-intolerant asthma (AIA) is characterized by moderate to severe asthma that is aggravated by aspirin or other non-steroidal anti-inflammatory drugs. Affected patients frequently have chronic rhinosinusitis and nasal polyposis due to persistent upper and lower airway inflammation with marked eosinophilia. IL-13 plays a crucial role in the development of allergic asthma by inducing airway eosinophilia and hyper-reactivity and it has been correlated with an increased eosinophil count. METHODS: Two promoter polymorphisms of the IL-13 gene (-1510 A>C and -1055C>T) and one coding nonsynonymus Arg110Gln (110G>A) polymorphism were genotyped using primer extension methods in 162 patients with AIA, 301 patients with aspirin-tolerant asthma (ATA), and 430 normal healthy controls (NC). RESULTS: There was no significant difference in the genotype, allele, and haplotype frequencies of the three polymorphisms among the three groups. AIA patients with the AA genotype -1510A>C (P=0.012) and CC genotype -1055C>T (PA). CONCLUSIONS: These findings suggest that the IL-13 polymorphisms at -1510A>C and 1055C>T are associated with the development of rhinosinusitis in AIA patients. IL-13 Arg110Gln may be associated with an increased eosinophil count and eotaxin-1 level and could increase eosinophilic inflammation in the upper and lower airways of patients with AIA.

IL-13 Gene Polymorphisms are Associated With Rhinosinusitis and Eosinophilic Inflammation in Aspirin Intolerant Asthma

PURPOSE: Aspirin-intolerant asthma (AIA) is characterized by moderate to severe asthma that is aggravated by aspirin or other non-steroidal anti-inflammatory drugs. Affected patients frequently have chronic rhinosinusitis and nasal polyposis due to persistent upper and lower airway inflammation with marked eosinophilia. IL-13 plays a crucial role in the development of allergic asthma by inducing airway eosinophilia and hyper-reactivity and it has been correlated with an increased eosinophil count. METHODS: Two promoter polymorphisms of the IL-13 gene (-1510 A>C and -1055C>T) and one coding nonsynonymus Arg110Gln (110G>A) polymorphism were genotyped using primer extension methods in 162 patients with AIA, 301 patients with aspirin-tolerant asthma (ATA), and 430 normal healthy controls (NC). RESULTS: There was no significant difference in the genotype, allele, and haplotype frequencies of the three polymorphisms among the three groups. AIA patients with the AA genotype -1510A>C (P=0.012) and CC genotype -1055C>T (PA). CONCLUSIONS: These findings suggest that the IL-13 polymorphisms at -1510A>C and 1055C>T are associated with the development of rhinosinusitis in AIA patients. IL-13 Arg110Gln may be associated with an increased eosinophil count and eotaxin-1 level and could increase eosinophilic inflammation in the upper and lower airways of patients with AIA.

Circulating Autoantibodies in Patients with Aspirin-intolerant Asthma: An Epiphenomenon Related to Airway Inflammation

Several studies have suggested the involvement of an autoimmune mechanism in aspirin (ASA)-intolerant asthma. To test this hypothesis, we measured the levels of circulating autoantibodies, such as IgG and IgA to tissue transglutaminase (TGase), IgG to cytokeratins (CKs) 8, 18, and 19, Clq-binding immune complex (CIC), and antinuclear antibody (ANA), in the sera of 79 patients with ASA-intolerant asthma (Group I) and those of two control groups, consisting of 61 patients with ASA-tolerant asthma (Group II) and 88 healthy control subjects (Group III) by means of ELISA. Significantly higher prevalences of IgG antibodies to CK18 (13.9%) and CK19 (17.7%) were noted in Group I, as compared with Group III (p<0.05 for all) not with Group II. Regarding the prevalences of other autoantibodies, the levels of ANA (1.3%), IgG to TGase (3.8%), and CIC (24.7%) in Group I were not significantly different from those in Groups II and III. Significant correlations were found between positivities for the anti-CK18 and anti-CK19 autoantibodies and the PC20 methacholine values in the analysis of asthma Groups I and II vs. normal controls, (p=0.001 and p=0.003, respectively). Further studies are needed to explore the potential involvement of an autoantibody-mediated mechanism in the clinical manifestation of bronchial asthma.

Lack of Association of Glutathione S-transferase P1 Ile105Val Polymorphism with Aspirin-Intolerant Asthma

BACKGROUND: Glutathion S-transferase P1 (GSTP1), the abundant isoform of glutathione S-transferase in lung epithelium, plays an important role in cellular protection against oxidative stress and toxic foreign chemicals. GSTP1 (Ile105Val) polymorphism has been reported to be associated with asthma related phenotypes such as atopy and bronchial hyperresponsiveness. Therefore we investigated whether this polymorphism may be associated with the development of aspirin-intolerant asthma (AIA). METHODS: GSTP1 Ile105Val polymorphism was determined using a single based extension method in 88 AIA subjects and compared to 154 aspirin-tolerant asthma (ATA) subjects and 119 normal healthy controls (NC) recruited from the Korean population. RESULTS: No significant differences in allele and genotype frequencies of the GSTP1 Ilel105Val polymorphism were observed in the three groups (p> 0.05). However, minor G allele frequency of the GSTP1 Ilel105Val polymorphism in AIA group (16.5%) tended to be lower than in the NC group (20.6%). CONCLUSION: These results suggest a lack of association of the GSTPI Ilel105Val gene polymorphism with AIA phenotype in the Korean population [word count: 159].

Differences in MMP-2, MMP-9, TIMP-1, and eosinophil inflammatory markers of nasal polyp homogenates between aspirin intolerant and tolerant asthma / 천식및알레르기

BACKGROUND AND OBJECTIVE: Nasal polyps are frequently found in patients with aspirin intolerant asthma (AIA). Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are thought to play a crucial role in airway inflammation and remodeling. Eosinophil and mast cell infiltration is a consistent finding in these polyps but few studies have studied the relationship between these cells and protease-antiprotease balance in the nasal polyp tissue of aspirin intolerant asthmatics. Our purpose was to compare the differences of eosinophil cationic protein (ECP), tryptase, MMP-2, MMP-9, and TIMP-1 between aspirin intolerant and tolerant asthmatics (ATA) and also to evaluate the relationship with inflammation in nasal polyp homogenates. MATERIALS AND METHODS: Nasal polyp tissue homogenates from 10 AIA subjects (group I) and 10 ATA subjects (group II) were compared. Inflammatory cell markers such as ECP and tryptase were measured by the CAP system (Pharmacia, Sweden). MMP-2, MMP-9, and TIMP-1 levels were measured by ELISA (Biotrack, UK). RESULTS: ECP levels were significantly higher in group I (p 0.05) and no significant differences were noted between MMP-2 levels between the two groups. MMP-9/TIMP-1 ratio was lower in group I than group II although this was not significant, and there were significant correlations between ECP, and MMP-9 (r=0.65, p < 0.05), MMP-2 (r=0.61, p < 0.05), and tryptase (r=0.58, p < 0.05), but not with TIMP-1. Significant correlations were also noted between tryptase, and MMP-9 (r=0.62, p < 0.05), and MMP-2 (r=0.47, p < 0.05), but not with TIMP-1. CONCLUSION: Nasal polyps from AIA patients had more severe eosinophilic inflammation compared to ATA subjects. MMP-9 and MMP-2 may contribute to eosinophil migration and inflammation.