PURPOSE: Leukotriene receptor antagonists (LTRAs) are used to treat aspirin-intolerant asthma (AIA); however, the protective effects of long-term LTRA administration against aspirin-induced bronchospasm have not been evaluated. OBJECTIVES: We investigated the efficacy of a 12-week treatment with a LTRA in protecting against aspirin-induced asthma in AIA patients. METHODS: Fifty-two adult patients with AIA underwent an aspirin challenge test just before administration of montelukast (10 mg/day) and just after 12 weeks of treatment. The protective effect was assessed as the disappearance of aspirin-induced bronchospasm after 12 weeks of treatment. The results were compared according to the patients' clinical and physiological parameters. RESULTS: The decline in FEV1 following aspirin challenge was significantly reduced from 28.6+/-1.9% to 10.2+/-1.7% (P=0.0001) after 12 weeks of montelukast treatment. However, 14 subjects (30%) still showed a positive response (>15% decline in FEV1) to aspirin challenge. Grouping the subjects into good and poor responders according to post-treatment responses revealed that the pretreatment aspirin-induced FEV1 decline was significantly greater in the poor responders and that the triggering dose of aspirin and the induction time for a positive response were lower and shorter, respectively, in the poor responders. Histories of aspirin hypersensitivity and sinusitis were more prevalent among the poor responders than among the good responders. CONCLUSIONS: Twelve weeks of treatment with montelukast protected against aspirin-induced bronchospasm in 70% of the AIA cases. A poor response was associated with more severe aspirin-induced bronchospasms before treatment and a history of aspirin hypersensitivity or sinusitis. CLINICAL IMPLICATIONS: A severe response to aspirin challenge may be a predictor of poor responsiveness to leukotriene antagonist treatment.
Acetates ; Adult ; Aspirin ; Asthma ; Asthma, Aspirin-Induced ; Bronchial Spasm ; Eosinophils ; Humans ; Hypersensitivity ; Leukotriene Antagonists ; Quinolines ; Receptors, Leukotriene ; Sinusitis

BACKGROUND: While aspirin sensitivity has been known to be common among patients with severe asthma, its frequency among asthmatics with mild to moderate severity remains to be learned. OBJECTIVES: To elucidate the frequency of aspirin sensitivity and its clinical characteristics among asthma patients with mild to moderate severity. MATERIAL AND METHODS: A total of 96 asthmatics with mild to moderate severity were enrolled. They underwent lysine-aspirin and methacholine bronchial provocation tests, and gave their induced sputum after the lysine-aspirin challenge. RESULTS: FEV1 declined greater than 20% compared with baseline FEV1 in 11 of 96 patients on the lysine-aspirin challenge. The frequency of aspirin sensitivity was higher among patients with enhanced bronchial hyperresponsiveness to methacholine (PC20 < 1 mg/ml) than among those without it (27.3% vs. 6.8%). The frequency was also higher in those with induced sputum eosinophil count higher than 3% than among those without it (38.9% vs. 0%). However, it was not associated with other risk factors such as age, sex, atopy, nasal polyps, and rhinosinusitis. CONCLUSION: More than 10% of mild to moderate asthmatics have aspirin sensitivity even though they have experienced no history of aspirin sensitivity which may be related with bronchial hyperresponsiveness to methacholine and eosinophil activation.
Aspirin* ; Asthma ; Asthma, Aspirin-Induced ; Bronchial Provocation Tests ; Eosinophils ; Humans ; Methacholine Chloride ; Nasal Polyps ; Prevalence* ; Risk Factors ; Sputum

BACKGROUND: Aspirin/NSAIDs can release cysteinyl-leukotriene (cys-LTs) into airways and precipitate asthmatic symptoms in aspirin - induced asthma(AIA). It has been reported that there is profound overexpression of LTC4 synthase in their bronchial mucosa, compared to aspirin-tolerant asthma. Objective : We observed whether genetic polymorphism of LTC4 synthase may be predisposed to LTC4 synthase overexpression in AIA. Subject and METHOD: Forty - four AIA patients having positive responses on lysin aspirin bron choprovocation tests and 47 non - aspirin induced asthma ( non - AIA ) patients having negative challenges and 32 healthy controls were enrolled. The genotypes of the promoter LTC4 synthase gene ( A,C transversion ) were determined by polymerase chain reaction and restriction fragment length polymorphism ( RFLP ) method. RESULTS: LTC4 synthase promoter polymorphism ( A444C btransversion) was not significantly different between non - AIA and AIA patients (p>0.05). Conclusion These findings suggest that genetic polymorphism of LTC4 synthase promoter may not be predisposed to LTC, synthase overexpression in AIA.
Aspirin* ; Asthma* ; Asthma, Aspirin-Induced ; Genotype ; Humans ; Leukotriene C4* ; Mucous Membrane ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

Omalizumab,as a biological agent targeting IgE,is a recombinant humanized monoclonal antibody and the first targeted drug approved for treating moderate-to-severe bronchial asthma.By reviewing one case of aspirin-induced asthma complicated with nasosinusitis and otitis media,we discussed the value of omalizumab in the treatment of asthma and its complications,aiming to provide a reference for clinical practice.
Humans ; Omalizumab/adverse effects* ; Asthma, Aspirin-Induced ; Asthma/drug therapy* ; Otitis Media/drug therapy*

Adult ; Aspergillosis, Allergic Bronchopulmonary ; etiology ; Aspirin ; adverse effects ; Asthma ; chemically induced ; diagnosis ; Humans ; Male ; Radiography, Thoracic ; Tomography, X-Ray Computed

Disodium cromoglycate(DSCG) has been widely used in the treatment of bronchial asthma and has become the prophylactic drug of choice in patients with mild-to-moderate asthma, because it has anti-allergic, anti-inflammatory and mast cell stabilizing properties. DSCG has been considered one of the safest medications among drugs for asthma treatment. The most common side effects are irritation of throat and dry mouth. Bronchospasm and chest tightness have been reported, but they were usually experienced by patients using spinhaler powdered capsules rather than metered dose inhalers (MDI). In this report, we presented a case of recurrent DSCG-induced bronchoconstriction with brief review of the literature. He had had an aspirin-induced asthma and had been well controlled with steroid inhalers and DSCG-MDI. After aspirin-bronchopro vocation test, he complained of chest discomfort and tightness immediately after inhaling DSCG-MDI. On serial monitoring of peak expiratory flow rate (PEER), there was a significant decline of PEER after two puffs inhalation of DSCG-MDI. Thus we performed DSCG-inhalation broncho provocation test with the nebulizer solution, which was pure DSCG without any addition of ingradients or propellants. This produced an early asthmatic reaction with more than 40% decline of FEV,. He was diagnosed as DSCG-induced bronchoconstriction and his clinical conditions were improved after avoidance of DSCG-MDI.
Asthma* ; Asthma, Aspirin-Induced ; Bronchial Spasm ; Bronchoconstriction* ; Capsules ; Humans ; Inhalation ; Mast Cells ; Metered Dose Inhalers ; Mouth ; Nebulizers and Vaporizers ; Occupations ; Peak Expiratory Flow Rate ; Pharynx ; Thorax

BACKGROUND/AIMS: Many patients with aspirin-induced asthma have severe methacholine airway hyperresponsiveness (AHR), suggesting a relationship between aspirin and methacholine in airway response. This study was performed to determine whether methacholine AHR affects the response of asthmatics to inhaled aspirin. METHODS: The clinical records of 207 asthmatic patients who underwent inhalation challenges with both aspirin and methacholine were reviewed retrospectively. An oral aspirin challenge was performed in patients with a negative inhalation response. The bronchial reactivity index (BRindex) was calculated from the percent decrease in lung function divided by the last dose of the stimulus. RESULTS: Forty-one (20.9%) and 14 (7.1%) patients showed a positive response to aspirin following an inhalation and oral challenge, respectively. Only 24.3 and 14.3% of the responders had a history of aspirin intolerance, respectively. The methacholine BRindex was significantly higher in the inhalation responders (1.46 +/- 0.02) than in the oral responders (1.36 +/- 0.03, p < 0.01) and in non-responders (n = 141, 1.37 +/- 0.01, p < 0.001). The aspirin BRindex was significantly correlated with the methacholine BRindex (r = 0.270, p < 0.001). Three of four patients who received the oral challenge, despite a positive inhalation test, showed negative responses to the oral challenge. Two of these patients had severe AHR. CONCLUSIONS: A considerable number of asthmatic patients with no history of aspirin intolerance responded to the inhalation aspirin challenge. The airway response to aspirin was significantly correlated with methacholine-AHR, and a false-positive response to aspirin inhalation test seemed to occur primarily in patients with severe AHR.
Administration, Inhalation ; Adolescent ; Adult ; Aspirin/*administration & dosage/*adverse effects ; Asthma/*physiopathology ; Asthma, Aspirin-Induced/etiology/physiopathology ; Bronchial Hyperreactivity/physiopathology ; Bronchial Provocation Tests ; Drug Hypersensitivity/etiology/physiopathology ; Female ; Humans ; Male ; Methacholine Chloride/*administration & dosage ; Retrospective Studies ; Young Adult

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

To investigate the pathogenic mechanism of late asthmatic response in comparison to early asthmatic response, changes of serum neutrophil chemotactic activity (NCA) using the Boyden chamber method and histamine level using the automated fluorometric analyzer were observed in 13 aspirin (ASA)-sensitive asthma subjects (group I: 7 early responders and group II: 6 dual responders) during lysine aspirin bronch-oprovocation test (L-ASA BPT). Sera were collected before, and 30 min and 240 min after L-ASA BPT. Serum NCA increased significantly after 30 min (p=0.02) and decreased significantly at 240 min (p=0.02) in group I, while serum NCA of group II increased significantly at 30 min (p=0.04), tending to increase further up to 240 min with no statistical significance. NCA at 240 min in group II subjects was significantly higher than baseline NCA (p=0.02). The serum NCAs collected before and 240 min were significantly higher in group II than in group I (p<0.05, respectively). There were no significant changes in serum histamine levels during L-ASA BPT in both groups. NCA derived from mast cell may contribute to the development of early asthmatic response induced by L-ASA inhalation. There may be a possible involvement of NCA derived from mononuclear cells during late asthmatic response.
Adult ; Aged ; Aspirin/adverse effects ; Aspirin/diagnostic use* ; Asthma/blood* ; Asthma/chemically induced ; Bronchial Provocation Tests* ; Chemotactic Factors/blood* ; Chemotactic Factors/secretion ; Chemotaxis/drug effects* ; Comparative Study ; Female ; Histamine/blood ; Human ; Interleukin-8/antagonists & inhibitors ; Interleukin-8/physiology ; Lysine/diagnostic use* ; Male ; Mast Cells/secretion ; Methacholine Chloride/diagnostic use ; Middle Aged ; Monocytes/secretion ; Neutrophils/drug effects* ; Time Factors

Aspirin exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyposis and aspirin hypersensitivity. The aspirin-induced bronchospasm is mediated by mast cell and eosinophilic inflammation. Recently, it has been reported that the expression of discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is up-regulated in lung cancers and is regulated by transcription factor AP-2 alpha (TFAP2A), a component of activator protein-2 (AP-2) that is known to regulate IL-8 production in human lung fibroblasts and epithelial cells. To investigate the associations between AERD and DCBLD2 polymorphisms, 12 common variants were genotyped in 163 AERD subjects and 429 aspirin tolerant asthma (ATA) controls. Among these variants, seven SNPs (rs1371687, rs7615856, rs828621, rs828618, rs828616, rs1062196, and rs8833) and one haplotype (DCBLD2-ht1) show associations with susceptibility to AERD. In further analysis, this study reveals significant associations between the SNPs or haplotypes and the percentage of forced expiratory volume in one second (FEV1) decline following aspirin challenge using multiple linear regression analysis. Furthermore, a non-synonymous SNP rs16840208 (Asp723Asn) shows a strong association with FEV1 decline in AERD patients. Although further studies for the non-synonymous Asp723Asn variation are needed, our findings suggest that DCBLD2 could be related to FEV1-related phenotypes in asthmatics.
Adolescent ; Adult ; Aged ; Alleles ; Asian Continental Ancestry Group/*genetics ; Aspirin/*adverse effects ; Asthma, Aspirin-Induced/etiology/*genetics ; Female ; Forced Expiratory Volume/drug effects/genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Male ; Membrane Proteins/*genetics ; Middle Aged ; *Polymorphism, Single Nucleotide ; Regression Analysis ; Republic of Korea ; Risk Factors ; Young Adult