SummaryBackground Toluene diisocyanate (TDI) is the most important cause of occupational asthma, but the genetic mechanism of TDI-induced asthma is still unknown. Objective The objective of the study was to identify susceptibility alleles associated with the TDI-induced asthma phenotype. Methods We conducted a genome-wide association study in 84 patients with TDI-induced asthma and 263 unexposed healthy normal controls using Affymetrix 500K SNPchip. We also investigated the relationships between genetic polymorphisms and transcript levels in Epstein-Barr virus-transformed lymphoblastoid cell lines from patients with TDI-induced asthma enrolled in this study. Results Genetic polymorphisms of CTNNA3 (catenin alpha 3, alpha-T catenin) were significantly associated with the TDI-induced asthma phenotype (5.84Â10À6 for rs10762058, 1.41Â10 À5 for rs7088181, 2.03Â10 À5 for rs4378283). Carriers with the minor haplotype, HT2 [GG], of two genetic polymorphisms (rs10762058 and rs7088181) showed significantly lower PC 20 methacholine level (P = 0.041) and lower mRNA expression of CTNNA3 than non-carriers (P = 0.040). A genetic polymorphism in the 3 0 downstream region of CTNNA3 (rs1786929), as identified by DNA direct sequencing, was significantly associated with the TDI-induced asthma phenotype (P = 0.015 in recessive analysis model) and the prevalence of serum-specific IgG to cytokeratin 19 (P = 0.031). Conclusion These findings suggested that multiple genetic polymorphisms of CTNNA3 may be determinants of susceptibility to TDI-induced asthma.

SummaryBackground Nasal polyps infiltrated with eosinophils are commonly found in chronic asthmatic patients, more frequently in those with aspirin-intolerant asthma (AIA) than aspirin-tolerant asthma (ATA). Some studies have suggested a contribution of superantigens derived from Staphylococcus sp to nasal polyposis and eosinophilia, but their relative importance in AIA and ATA subjects is unknown. Objective We investigated whether local production of specific IgE to staphylococcal enterotoxins A and B (SEA and SEB) and relationships with markers of eosinophilic inflammation differ in the nasal polyps of AIA and ATA subjects. Methods Fifteen AIA subjects with positive responses to lysine-aspirin bronchoprovocation and 15 ATA subjects underwent polypectomy. Immunoassays were used to quantify eosinophil cationic protein (ECP), IL-5, mast cell tryptase, soluble IL-2 recepters (sIL-2R), total IgE, and specific IgE for SEA and SEB. Results ECP levels in nasal polyp homogenates were higher in AIA subjects than in ATA subjects (Po0.02), with no significant differences in tryptase, IL-5 or sIL-2R. Total IgE, and specific IgE to both SEA and SEB, were detectable in some nasal polyps from both subject groups, but median levels were markedly higher in AIA subjects than in ATA subjects (P 5 0.04, 0.01, 0.05, respectively). Levels of specific IgE to SEA and SEB correlated significantly with levels of ECP and IL-5, but not those of tryptase or sIL-2R. Conclusion These findings suggest that staphylococcal superantigens may drive local eosinophilic inflammation in nasal polyp tissue, and that this is exacerbated in subjects with AIA.

We found four distinct subtypes with different clinical/biochemical findings and asthma exacerbations in a NERD cohort. These findings suggest that stratified strategies by applying subtype classification may help achieve better outcomes in the management of NERD.

Vertebroplasty using polymethylmethacrylate (PMMA) for augmentation is accepted as a safe and effective treatment for vertebral compression fracture. However, various complications related to PMMA vertebroplasty have recently been reported. We experienced three cases with progressive collapse of PMMA-augmented vertebra. Collapse progressed after augmentation in cases where PMMA conglomerated without contiguous bone interdigitation. A high viscosity of the PMMA preparation and vertebral body cavitory lesion may play a role in progressive vertebral collapse. To avoid this complication, bone cement should be injected sufficiently and permeate to contiguous bone to create strong support and anchorage.