The pathogenesis of aspirin-exacerbated respiratory disease (AERD) is characterized by the low expression of cyclooxygenase-2 (COX-2) in airway epithelia, which decreases the production of prostaglandin E2 (PGE2). Conversely, cigarette smoke stimulates COX-2 expression in airway epithelia. Therefore, it was hypothesized that the development of AERD would be suppressed by elevated PGE2 levels in smokers, and smoking cessation might increase susceptibility to AERD.The objective of this study was to evaluate the relationship between smoking and the risk of AERD development.The smoking status of patients with AERD (n = 114) was compared with 2 control groups with aspirin-tolerant asthma (ATA), patients diagnosed by a systemic aspirin provocation test (ATA-1, n = 83) and outpatients randomly selected from a large-scale dataset (ATA-2, n = 914), as well as a healthy control group (HC, n = 2313).At the age of asthma onset, there was a low frequency of current smokers (9.7%), but a high frequency of past smokers (20.2%) in the AERD group compared with the ATA-1 (20.5% and 12.0% for current and past smokers, respectively), ATA-2 (24.5% and 10.3%, respectively), and HC group (26.2% and 12.6%, respectively). After adjustment for confounding variables, AERD was positively associated with smoking cessation between 1 and 4 years before disease onset compared with the ATA-2 group (adjusted odds ratio [aOR] 4.63, 95% confidence interval [CI]: 2.16-9.93) and the HC group (aOR 4.09, 95% CI: 2.07-8.05), implying that smoking cessation was followed by the development of AERD.Smoking cessation may be a risk factor for the development of AERD.
Aspirin-exacerbated respiratory disease (AERD) is characterized by the triad of asthma, eosinophilic nasal polyposis and a hypersensitivity to all medications that inhibit the cyclo- oxygenase (COX) -1 enzyme. Clinical history and observed aspirin provocation test remains gold standard for diagnosis of AERD. AERD patients typically have more severe asthma with airflow limitation and greater requirement for high-dose corticosteroid therapies. Over- production of cysteinyl-leukotrienes (CysLTs) and prostaglandin D2 (PGD2) correlate with the pathogenetic features of AERD, suggesting the possible involvement of mast cell activation with innate type 2 immune response. Next breakthroughs in diagnosis and treatment have been expected in the nearest futures.
Aims: To investigate a role of helper T (Th) cells in asthma, T cell-transfer model was analyzed for late phase asthmatic response. Methods: Ovalbumin (OVA) specific Th clones were derived from either the regional lymphnodes of Balb/c mice immunized with OVA/CFA or splenocytes of DO11.10 transgenic mice expressing T cell receptor specific for OVA/H-2d. Th clones were adoptively transferred into unprimed mice. After antigen challenge, airway resistance was continuously monitored by either unrestrained whole body plethysmography(BUXCO) or resistance/compliance analyzer under anesthetized condition. Bronchoalveolar lavage analysis was performed 48 hr after OVA challenge. Supernatants of stimulated Th clones were analyzed for contractile activity using collagen gels embedded with murine primary bronchial smooth muscle cells. Effects of H1R and LTR1 antagonist were analyzed both in vitro and in vivo. Results: When unprimed mice were transferred with Th clones, T5-1, T6-2, T6-4, and T6-7, Penh values were significantly increased 6 hr after challenge with OVA or T cell epitope peptide, OVA323-339. In contrast, mice transferred with other Th clones, BF7, T6-1, or T6-10 did not show any change. Airflow limitation was confirmed by a direct measurement of airway resistance under anesthetized, restrained, and intubated conditions. Contractile activity was detected in the supernatants of T6-2 stimulated with immobilized anti-CD3. T cell-induced contraction was not affected by H1R or LTR1 antagonist. Conclusion: Activation of Th cells resulted in an airflow limitation besides eosinophilic inflammation, AHR, and mucous hyperplasia. T cell-derived bronchoconstrictor might be a target for treatment-resistant asthma.
The bronchial hyperresponsiveness (BHR) test is useful to diagnose or evaluate effect of therapy in asthmatics, but invasive. On the other hands, the fraction of exhaled nitric oxide (FENO) is a useful noninvasive marker of eosinophilic airway inflammation in asthmatics. And also, the forced oscillation technique (FOT) is a noninvasive method that is used to measure respiratory mechanics, including respiratory resistance and reactance at multiple frequencies.To evaluate the complementary roles of FENO and FOT to predict bronchial hyperresponsiveness in adult stable asthmatic patients taking inhaled corticosteroids.From our outpatient clinic, we recruited 115 stable asthmatics that were being treated with inhaled corticosteroids at the time of the study. For each subject, we measured FENO by using an offline methods (CEIS' method); and we measured resistance at 5Hz (R5), resistance at 20Hz (R20), R5-R20, reactance at 5Hz (X5), frequency of resonance (Fres), and low-frequency reactance area (ALX), by using a MostGraph FOT machine. We also used spirometry to test BHR to acetylcholine (PC20Ach).LogPC20Ach was significantly correlated with FENO, R5, R20, R5-R20 and %FEV1. The ROC curve decided that the cutoff point of FENO was 37.8ppb (AUC=0.647, sensitivity 83.3%, specificity 55.6%, p=0.007) and that of R5 was 3.03cmH2O/L/S (AUC=0.684, sensitivity 72.2%, specificity 52.8%, p=0.001) and that of R20 was 2.77cmH2O/L/S (AUC=0.684, sensitivity 74.5%, specificity 59.4%, p=0.001). When R5 was >3.03 and FENO was >37.8ppb, 25 of 38 subjects (65.7%) had bronchial hyperresponsiveness. If R5 was <3.03 and FENO was <37.8 ppb, only 5 of 29 (17.2%) subjects had. When R20 was >2.77 and FENO was >37.8ppb, 29 of 43 subjects (67.4%) had bronchial hyperresponsiveness. If R20 was <3.03 and FENO was <37.8ppb, only 2 of 18 (11.1%) subjects had.Combining R5 or R20 and FENO can predict the level of bronchial hyperresponsiveness in adult stable asthmatics.
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