Aspirin and food additives are known to induce bronchoconstriction, angioedema or urticaria in susceptible patients. To evaluate the incidence of hypersensitivity to aspirin and food additives, 36 subjects with bronchial asthma, 33 of whom were non-allergic asthmatics and 3 were allergic asthmatics who had a history of aspirin sensitivity, were challenged orally with six compounds: acetylsalicylic acid (ASA), sodium bisulfite, tartrazine, sodium benzoate, 4-hydroxy benzoic acid, and monosodium L-glutamate. Significant bronchoconstrictions were found in 15 (41.7%) of the 36 subjects tested. Eight of the 15 subjects showed positive asthmatic responses to the aspirin, two showed asthmatic responses to the food additives, and five responded to both aspirin and the food additives. It is suggested that ASA and food additives could be causes of clinically significant bronchoconstriction in moderately severe non-allergic asthmatic patients.
Adolescent ; Adult ; Aged ; Aspirin/*immunology ; Asthma/*immunology ; Bronchial Provocation Tests/*methods ; Drug Hypersensitivity/*immunology ; Female ; Food Additives/*adverse effects ; Human ; Male ; Middle Age

Aspirin and food additives are known to induce bronchoconstriction, angioedema or urticaria in susceptible patients. To evaluate the incidence of hypersensitivity to aspirin and food additives, 36 subjects with bronchial asthma, 33 of whom were non-allergic asthmatics and 3 were allergic asthmatics who had a history of aspirin sensitivity, were challenged orally with six compounds: acetylsalicylic acid (ASA), sodium bisulfite, tartrazine, sodium benzoate, 4-hydroxy benzoic acid, and monosodium L-glutamate. Significant bronchoconstrictions were found in 15 (41.7%) of the 36 subjects tested. Eight of the 15 subjects showed positive asthmatic responses to the aspirin, two showed asthmatic responses to the food additives, and five responded to both aspirin and the food additives. It is suggested that ASA and food additives could be causes of clinically significant bronchoconstriction in moderately severe non-allergic asthmatic patients.
Adolescent ; Adult ; Aged ; Aspirin/*immunology ; Asthma/*immunology ; Bronchial Provocation Tests/*methods ; Drug Hypersensitivity/*immunology ; Female ; Food Additives/*adverse effects ; Human ; Male ; Middle Age

Thyroid antibodies are frequently observed in urticaria patients, but their roles in urticaria are not clearly elucidated. We investigated the role of serum specific IgE to thyroid peroxidase (TPO) in patients with aspirin intolerant acute urticaria (AIAU) and aspirin intolerant chronic urticaria (AICU). We recruited 59 AIAU and 96 AICU patients with 69 normal controls (NC). Serum specific IgE to TPO was measured by manual direct ELISA, and CD203c expressions on basophil with additions of TPO were measured to prove a direct role of TPO in effector cells. The prevalences of serum specific IgE to TPO were significantly higher in AIAU (15.2%) and AICU groups (7.5%) compared to NC (0%, P=0.018: P=0.013, respectively). Flow cytometry showed CD203c induction in a dose dependent manner with serial additions of TPO in some AIAU and AICU patients having high specific IgE to TPO. Our findings show that the prevalence of serum specific IgE to TPO was significantly higher in both AIAU and AICU patients than in NC. It is suggested that specific IgE to TPO play a pathogenic role in AIAU and AICU.
Adult ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Aspirin/*adverse effects ; Autoantibodies/immunology ; Basophils/drug effects/*immunology ; Humans ; Immunoglobulin E/blood/*immunology ; Iodide Peroxidase/blood/*immunology ; Urticaria/*chemically induced/*immunology/pathology

BACKGROUNDThe management of patients with recurrent miscarriage (RM) and antiphospholipid antibody syndrome (APS) includes prolonged treatment with heparin and aspirin, starting from the confirmation of pregnancy and continuing until 6 weeks after birth. This study was conducted to determine the relationship between changes in antiphospholipid antibody titers and clinical outcomes. The effect of a shortened treatment regimen was also evaluated.

METHODSA prospective study of 123 patients with RM and APS between March 2012 and May 2014 was conducted. Patients were pretreated with a low dose of prednisone plus aspirin before pregnancy, and heparin was added after conception. The levels of antiphospholipid antibodies and pregnancy outcomes were evaluated.

RESULTSAll patients were positive for anti-β2-glycoprotein 1 (anti-β2-GP1) IgM. After prepregnancy treatment with low-dose prednisone plus aspirin, 99 of 123 patients became pregnant, and 87 of those pregnancies resulted in successful live births, while 12 resulted in miscarriage, showing a success rate of 87.9%. In the live birth group, levels of anti-β2-GP1 were 56.8 ± 49.0 RU/ml before the pretreatment regimen, 32.1 ± 26.0 RU/ml after 2 months of pretreatment, and 24.1 ± 23.1 RU/ml during early pregnancy (P < 0.05). In the miscarriage group, antiphospholipid antibody titers were 52.8 ± 30.7 RU/ml before pretreatment, 38.5 ± 34.2 RU/ml after pretreatment, and 33.9 ± 24.7 RU/ml during early pregnancy; the decrease in antiphospholipid antibodies was lower in the miscarriage group than in the live birth group (P < 0.05). Of the 24 infertile patients, the average antibody titer did not decline after pretreatment (P = 0.802).

CONCLUSIONSAnti-β2-GP1 IgM was the predominant form of antibody in patients with RM and APS. The decreases in antiphospholipid antibody titers correlated with better pregnancy outcomes. The shorter treatment regimen was effective and economical.

Abortion, Habitual ; immunology ; prevention & control ; Adult ; Antibodies, Antiphospholipid ; immunology ; Anticoagulants ; therapeutic use ; Antiphospholipid Syndrome ; drug therapy ; immunology ; Aspirin ; therapeutic use ; Female ; Heparin ; therapeutic use ; Humans ; Live Birth ; Prednisone ; therapeutic use ; Pregnancy ; Pregnancy Complications ; prevention & control ; Pregnancy Outcome ; Prospective Studies

Aspirin intolerant asthma (AIA) is frequently characterized as an aspirin (ASA)-exacerbated respiratory disease (AERD). It is a clinical syndrome associated with chronic severe inflammation in the upper and lower airways resulting in chronic rhinitis, sinusitis, recurrent polyposis, and asthma. AERD generally develops secondary to abnormalities in inflammatory mediators and arachidonic acid biosynthesis expression. Upper and lower airway eosinophil infiltration is a key feature of AERD; however, the exact mechanisms of such chronic eosinophilic inflammation are not fully understood. Cysteinyl leukotriene over-production may be a key factor in the induction of eosinophilic activation. Genetic studies have suggested a role for variability of genes in disease susceptibility and response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1* 301, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10 -1082A > G, ACE -262A > T, and CRTH2 -466T > C; the four-locus SNP set was composed of B2ADR 46A > G, CCR3 -520T > G, CysLTR1 -634C > T, and FCER1B -109T > C. Management of AERD is an important issue. Aspirin ingestion may result in significant morbidity and mortality, and patients must be advised regarding aspirin risk. Leukotriene receptor antagonists (LTRA) that inhibit leukotriene pathways have an established role in long-term AERD management and rhinosinusitis. Aspirin desensitization may be required for the relief of upper and lower airway symptoms in AERD patients. Future research should focus on identification of biomarkers for a comprehensive diagnostic approach.
Animals ; Asthma, Aspirin-Induced/drug therapy/*genetics/*immunology ; Eosinophils/metabolism ; Genetic Predisposition to Disease/genetics ; Humans ; Leukotriene Antagonists/therapeutic use ; Leukotrienes/metabolism ; Models, Biological ; Polymorphism, Genetic/genetics/physiology

BACKGROUND & OBJECTIVES: The pathogenic mechanism of aspirin-sensitive asthma (ASA-BA) remains to be further defined. To evaluate the role of circulating immune complex (CIC) in ASA-BA. SUBJECTS & METHODS: We measured IgG- and IgA-IC level by ELISA using anti-C3 antibody in 33 ASA-BA patients whose sensitivity was confirmed by lysine-aspirin bronchoprovocation test, and compared with those of 14 allergic, 14 intrinsic asthma patients and 7 healthy controls. RESULTS: There was no significant difference in IgG-IC level among the four groups (p > 0.05), while IgA-IC levels of aspirin-sensitive asthma were higher than those of other groups (p = 0.0035). Patients with nasal polyp had significantly higher IgG-IC than those without it (p = 0.02). No differences were found according to medication and symptom scores, and presence of atopy, rhino-sinusitis, urticaria or concurrent sensitivity to sulfite (p > 0.05). Insignificant correlation was found between IgG-IC level and asthma duration, total IgE level, or circulating eosinophil count. CONCLUSION: These findings suggest a possible contribution of IgG-IC to the development of nasal polyp in ASA-BA. Further study will be needed to clarify the role of IgA-IC in the pathogenesis of ASA-BA.
Adult ; Aged ; Antigen-Antibody Complex/blood* ; Aspirin/adverse effects* ; Asthma/immunology* ; Asthma/etiology* ; Asthma/complications ; Case-Control Studies ; Human ; IgA/blood ; IgG/blood ; Middle Age ; Nasal Polyps/etiology

Non-acetylated salicylates have been recommended for use as alternatives to nonsteroidal anti-inflammatory drugs (NSAIDs) in aspirin and/or tartrazine-sensitive patients. We experienced a case of an aspirin-sensitive asthmatic patient who developed a broncho-obstructive reaction after taking 100 mg of sodium salicylate. The result of this study suggests that sodium salicylate may cross-react with aspirin in aspirin-and tartrazine-sensitive patients.
Aspirin/*adverse effects/immunology ; Asthma/*complications/diagnosis/etiology ; Bronchial Provocation Tests ; Cross Reactions ; Drug Hypersensitivity/*complications/diagnosis/etiology ; Female ; Humans ; Middle Aged ; Sodium Salicylate/*adverse effects/immunology ; Tartrazine/adverse effects

It has been well established that bacterial superantigens lead to the induction and aggravation of chronic inflammatory skin diseases. We investigated the clinical significance of serum specific immunoglobulin E (lgE) to the staphylococcal superantigens staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B (SEB), and toxic shock syndrome toxin (TSST)-1 in patients with chronic urticaria (CU), focusing on the differences in these prevalences between aspirin-intolerant CU (AICU) and aspirin-tolerant CU (ATCU) patients. Aspirin sensitivity was confirmed by oral aspirin provocation test. There were 66 patients AICU and 117 patients ATCU in the study. Serum IgE antibodies specific for SEA, SEB, and TSST-1 were measured by the ImmunoCAP test and the patients were compared with 93 normal controls (NC). The prevalences of serum specific IgE to staphylococcal superantigens were significantly higher in CU than in NC patients (IgE to SEA, 13.7% vs. 5.4%; IgE to SEB, 12.0% vs. 4.3%; IgE to TSST-1, 18.0% vs. 6.5%; p<0.05, respectively). The patients with specific IgE to SEA, SEB, and TSST-1 had higher serum total IgE levels and higher rates of atopy. Significant associations were noted between the prevalence of specific IgE to SEA and SEB and the HLA DQB1*0609 and DRB1*1302 alleles in the AICU group. We confirmed that a sub-population of patients with CU possesses serum IgE antibodies to SEA, SEB, and TSST- 1. Particularly, the IgE immune response to TSST-1 is associated with aspirin sensitivity in CU patients.
Adolescent ; Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Antigens/*chemistry ; Aspirin/pharmacology ; Bacterial Toxins/metabolism ; Chronic Disease ; Enterotoxins/metabolism ; Female ; Humans ; Immunoglobulin E/*chemistry/metabolism ; Male ; Middle Aged ; Phenotype ; Staphylococcus/*genetics/immunology ; Superantigens/metabolism ; Urticaria/*immunology

In this study of the inhibitory effects of angiopeptin and aspirin on the development of accelerated graft atherosclerosis (AGAS), 22 B10.BR mice received intra-abdominal heterotopic heart transplants from B10.A mice, without immunosuppression. Group 1 (n = 5) received no pharmacological intervention, Group 2 (n = 6) was treated with angiopeptin, Group 3 (n = 5) with aspirin, and Group 4 (n = 6) with both. There was no significant difference in the incidence of AGAS among these groups. The magnitude of intimal lesion development showed less narrowing of large vessels (> 100 microns in diameter) in groups 2 and 4--i.e. the groups received angiopeptin (Group 1 = 46.9 +/- 9.3%, Group 2 = 28.5 +/- 9.2%, Group 3 = 44.1 +/- 10.9%, Group 4 = 24.2 +/- 5.9%; p < 0.01). Comparison of the fraction of tropomyosin-positive staining cells in the intima revealed a lesser degree of staining in Group 2 (p < 0.01). No intervention was effective in preventing smooth muscle cell proliferation in the media or inflammatory cell infiltration in the adventitia. In conclusion, our data suggest that angiopeptin is effective in the direct inhibition of intimal smooth muscle cell proliferation in relatively large vessels, whereas aspirin exhibits no inhibitory role in the progression of AGAS. Angiopeptin appears to be a potential therapeutic agent for inhibiting the progression of postoperative AGAS in clinical heart transplantation.
Animal ; Aspirin/pharmacology* ; Cardiovascular Agents/pharmacology* ; Coronary Arteriosclerosis/pathology ; Coronary Arteriosclerosis/immunology* ; Coronary Vessels/pathology ; Coronary Vessels/drug effects ; Heart/drug effects* ; Heart Transplantation/immunology* ; Immunohistochemistry ; Mice ; Mice, Inbred Strains ; Myocardium/pathology ; Myocardium/immunology ; Oligopeptides/pharmacology* ; Somatostatin/pharmacology ; Somatostatin/analogs & derivatives* ; Transplantation, Homologous/immunology ; Tropomyosin/metabolism

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.
Middle Aged ; Male ; Keratins/chemistry ; Inflammation ; Humans ; Female ; *Drug Resistance ; Child ; Case-Control Studies ; Bronchi/*pathology ; Autoantibodies/*chemistry ; Asthma/*drug therapy/*immunology ; Aspirin/*pharmacology ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Aged