Genetic variants with gene regulatory effects are associated with diisocyanate-induced asthma.

Background: Isocyanates are major causes of occupational asthma, but susceptibility and mechanisms of diisocyanate-induced asthma (DA) remain uncertain.

Objective: The aim of this study was to identify DA-associated functional genetic variants through next-generation sequencing (NGS), bioinformatics, and functional assays.

Methods: NGS was performed in 91 workers with DA.

Comparison of biological effects with albumin adducts of 4,4'-methylenediphenyl diisocyanate in workers.

Lung sensitization and asthma are the main health effects of 4,4'-methylenediphenyl diisocyanate (MDI). Albumin adducts (isocyanate-specific adducts) of MDI might be involved in the etiology of sensitization reactions. Albumin adducts of MDI were analyzed in sera of diisocyanate-exposed worker with and without diisocyanate occupational asthma (DA), as well as in exposed workers with and without diisocyanate-specific IgG antibodies.

N-Acetyltransferase 2 Genotypes Are Associated With Diisocyanate-Induced Asthma.

Objective: To investigate whether genetic variants of N-acetyltransferase (NAT) genes are associated with diisocyanate asthma (DA).

Methods: The study population consisted of 354 diisocyanate-exposed workers. Genotyping was performed using a 5'-nuclease polymerase chain reaction assay.

Genome-Wide Association Study Identifies Novel Loci Associated With Diisocyanate-Induced Occupational Asthma.

Diisocyanates, reactive chemicals used to produce polyurethane products, are the most common causes of occupational asthma. The aim of this study is to identify susceptibility gene variants that could contribute to the pathogenesis of diisocyanate asthma (DA) using a Genome-Wide Association Study (GWAS) approach. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed in 74 diisocyanate-exposed workers with DA and 824 healthy controls using Omni-2.

Early-life mold and tree sensitivity is associated with allergic eosinophilic rhinitis at 4 years of age.

Background: Nasal eosinophils are a biomarker for allergic rhinitis (AR) and are associated with increased symptom severity.

Objective: To identify predictors of allergic eosinophilic rhinitis (AER) in early childhood in children at higher risk for chronic allergic respiratory disorders.

Methods: In the Cincinnati Childhood Allergy and Air Pollution Study, infants born to aeroallergen-sensitized and symptomatic parents were examined and underwent skin prick testing (SPT) annually to 15 aeroallergens from 1 to 4 years of age.

Genetic variants in TNFα, TGFB1, PTGS1 and PTGS2 genes are associated with diisocyanate-induced asthma.

Diisocyanates are the most common cause of occupational asthma, but risk factors are not well defined. A case-control study was conducted to investigate whether genetic variants in inflammatory response genes (TNFα, IL1α, IL1β, IL1RN, IL10, TGFB1, ADAM33, ALOX-5, PTGS1, PTGS2 and NAG-1/GDF15) are associated with increased susceptibility to diisocyanate asthma (DA). These genes were selected based on their role in asthmatic inflammatory processes and previously reported associations with asthma phenotypes.

Genetic variants in the major histocompatibility complex class I and class II genes are associated with diisocyanate-induced Asthma.

Objective: To investigate the association between single nucleotide polymorphisms (SNPs) located across the major histocompatibility complex and susceptibility to diisocyanate-induced asthma (DA).

Methods: The study population consisted of 140 diisocyanate-exposed workers. Genotyping was performed using the Illumina GoldenGate major histocompatibility complex panels.

Chronic traffic pollution exposure is associated with eosinophilic, but not neutrophilic inflammation in older adult asthmatics.

Objective: Airway inflammatory patterns in older asthmatics are poorly understood despite high asthma-related morbidity and mortality. In this study, we sought to define the relationship between exposure to traffic pollutants, biomarkers in induced sputum, and asthma control in older adults.

Methods: Induced sputum was collected from 35 non-smoking adults ≥65 years with a physician's diagnosis of asthma and reversibility with a bronchodilator or a positive methacholine challenge.

Interferon-γ promoter is hypermethylated in blood DNA from workers with confirmed diisocyanate asthma.

Risk factors have not been identified that determine susceptibility for development of diisocyanate-induced occupational asthma (DA). We hypothesized that diisocyanate (DI) exposure could modify gene promoter regions regulating transcription of cytokine mediators and thereby influence expression of DA. A cross-sectional study was designed to investigate the promoter methylation status of candidate genes in DI-exposed workers.

CTNNA3 (α-catenin) gene variants are associated with diisocyanate asthma: a replication study in a Caucasian worker population.

Recently, a genome-wide association study (GWAS) conducted in Korean subjects identified four CTNNA3 (alpha-T catenin) single nucleotide polymorphisms (SNPs) (rs10762058, rs7088181, rs1786929, and rs4378283) associated with diisocyanate-induced occupational asthma (DA). The CTNNA3 gene codes for a cadherin involved in formation of stretch-resistant cell-cell adhesions. We conducted a candidate gene association study to replicate these findings in Caucasian workers.

Genetic variants in antioxidant genes are associated with diisocyanate-induced asthma.

Diisocyanates are a common cause of occupational asthma, but risk factors are not well defined. A case-control study was conducted to investigate whether genetic variants of antioxidant defense genes, glutathione S-transferases (GSTM1, GSTT1, GSTM3, GSTP1), manganese superoxide dismutase (SOD2), and microsomal epoxide hydrolase (EPHX1) are associated with increased susceptibility to diisocyanate-induced asthma (DA). The main study population consisted of 353 Caucasian French-Canadians from among a larger sample of 410 diisocyanate-exposed workers in three groups: workers with specific inhalation challenge (SIC) confirmed DA (DA(+), n = 95); symptomatic diisocyanate workers with a negative SIC (DA(-), n = 116); and asymptomatic exposed workers (AW, n = 142).

House dust bioactivities predict skin prick test reactivity for children with high risk of allergy.

Background: Although evidence suggests that ambient exposures to endotoxin and other immunostimulants during early life influence allergic risk, efforts to understand this host-environment relationship have been hampered by a paucity of relevant assays.

Objectives: These investigations determined whether parameters of house dust extract (HDE) bioactivity were predictive of allergen skin prick test (SPT) reactivity for infants at high risk of allergy participating in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS).

Methods: We conducted a nested case-control study, selecting 99 CCAAPS children who had positive SPT results to at least 1 aeroallergen at age 3 years and 101 subjects with negative SPT results.

Pathogenesis and disease mechanisms of occupational asthma.

Occupational asthma (OA) is one of the most common forms of work-related lung disease in all industrialized nations. The clinical management of patients with OA depends on an understanding of the multifactorial pathogenetic mechanisms that can contribute to this disease. This article discusses the various immunologic and nonimmunologic mechanisms and genetic susceptibility factors that drive the inflammatory processes of OA.

Cyanobacteria: an unrecognized ubiquitous sensitizing allergen?

This study was designed to investigate the prevalence of skin sensitization using detoxified cyanobacterial reagents in a chronic rhinitis population. Subjects ≥6 years of age who presented for allergy consultation to a community allergy practice and required skin-prick testing (SPT) to common seasonal and perennial aeroallergens were enrolled after signing an informed consent. Detoxified cyanobacteria species were used for skin testing.

A case of progesterone-induced anaphylaxis, cyclic urticaria/angioedema, and autoimmune dermatitis.

Objective: Women have exhibited anaphylaxis, urticaria/angioedema, and autoimmune progesterone dermatitis (APD) coinciding with the progesterone premenstrual rise. We report a detailed immunological evaluation of such a woman responsive to a gonadotropin hormone-releasing agonist (GHRA).

Methods: Skin testing, enzyme-linked immunosorbent assays (ELISAs), leukocyte histamine release (LHR), and inhibition assays were performed to demonstrate progesterone immunoresponsiveness.

Communities near toluene diisocyanate sources: an investigation of exposure and health.

Toluene diisocyanate (TDI) is a well-known cause of occupational asthma, but we know little about the potential for exposure and health effects among residents who live near facilities that release TDI. In the mid-1990's, the North Carolina Department of Health and Human Services and the Agency for Toxic Substances and Disease Registry investigated exposures to TDI and health outcomes in one community, which left some unanswered questions. This cross-sectional study evaluated the potential associations between living near a TDI source and the prevalence of three variables: asthma or asthma-like respiratory symptoms, antibodies specific to TDI, and verifiable levels of TDI in residential air.

Diisocyanate conjugate and immunoassay characteristics influence detection of specific antibodies in HDI-exposed workers.

Background: The structural characteristics of diisocyanate chemical protein antigens vary depending upon the methods of production, and may influence diisocyanate antigen immunoassays. The impact of different antigen preparation methods on immunoassay sensitivity, specificity, and predictive value for identifying workers with diisocyanate asthma (DA) has not been systematically evaluated.

Objective: Evaluate the influence of preparation methodology of hexamethylene diisocyanate human serum albumin (HDI-HSA) conjugates on the performance of specific antibody assays for identifying workers with confirmed HDI asthma.

Influence of dog ownership and high endotoxin on wheezing and atopy during infancy.

Background: Increased exposure to microbial products early in life may protect from development of atopic disorders in childhood. Few studies have examined the relationship of endotoxin exposure and pet ownership on atopy and wheezing during infancy.

Objective: Evaluate relationships among high endotoxin exposure, pet ownership, atopy, and wheezing in high-risk infants.

Evaluation of antibody binding to diisocyanate protein conjugates in a general population.

Background: Specific IgG binding to diisocyanate-human serum albumin (HSA) has been proposed as an indicator of diisocyanate exposure. One residential study reported IgG binding to diisocyanate conjugates in 8% of residents living near a factory using toluene diisocyanate (TDI). Because comparable assays were not performed using individuals distant from such facilities, the significance of this finding is uncertain.

Quantitative PCR analysis of house dust can reveal abnormal mold conditions.

Indoor mold concentrations were measured in the dust of moldy homes (MH) and reference homes (RH) by quantitative PCR (QPCR) assays for 82 species or related groups of species (assay groups). About 70% of the species and groups were never or only rarely detected. The ratios (MH geometric mean : RH geometric mean) for 6 commonly detected species (Aspergillus ochraceus, A.

Advances in methods used in evaluation of occupational asthma.

Purpose Of Review: Diagnosing occupational asthma (OA) is a complex undertaking, the primary goal of which is to demonstrate a causal relation between exposure to a specific agent encountered at work and asthmatic responses. Recent development or refinement of diagnostic tools may improve the diagnostic accuracy, which may have important economic and social consequences for both employers and workers.

Recent Findings: Although specific inhalation challenge (SIC) testing is the gold standard for diagnosis of OA, these tests are not widely available in many countries.

Diisocyanate antigen-stimulated monocyte chemoattractant protein-1 synthesis has greater test efficiency than specific antibodies for identification of diisocyanate asthma.

We previously reported that diisocyanate-human serum albumin (DIISO-HSA) stimulated production of monocyte chemoattractant protein-1 (MCP-1) by peripheral blood mononuclear cells is significantly associated with a clinical diagnosis of diisocyanate asthma (DA). Others have reported that antibodies for DIISO-HSA are specific but insensitive markers of DA. This study was performed to evaluate test characteristics of the in vitro MCP-1 assay compared with DIISO-HSA-specific immunoglobulin (Ig) G and IgE in identifying workers with DA.

Exposure to protein aeroallergens in egg processing facilities.

Proteinaceous materials in the air can be highly allergenic and result in a range of immunologically mediated respiratory effects, including asthma. We report on the largest evaluation of exposure to date of airborne egg protein concentrations in an egg breaking and processing plant that had cases of occupational asthma. Personal air samples for egg protein were analyzed in duplicate on each PTFE filter using two analytical methods: (1) a commercial assay for non-specific total protein, and (2) indirect competitive inhibition assay using an ELISA method to quantify specific egg protein components.