Apoptosis signal-regulating kinase 1 (ASK1) is an upstream signaling molecule in oxidative stress-induced responses. Because oxidative stress is involved in asthma pathogenesis, ASK1 gene deficiency was investigated in animal models of allergic asthma. However, there is no study to investigate whether ASK1 inhibitors could be applied for asthma to date. Selonsertib, a potent and selective ASK1 inhibitor, was applied to BALB/c mice of an ovalbumin (OVA)-induced allergic asthma model. Selonsertib suppressed antigen-induced degranulation of RBL-2H3 mast cells in a concentration-dependent manner. The administration of selonsertib both before OVA sensitization and OVA challenge significantly reduced airway hyperresponsiveness, and suppressed eosinophil numbers and inflammatory cytokine levels in the bronchoalveolar lavage fluid. Histopathologic examination elucidated less inflammatory responses and reduced mucin-producing cells around the peribronchial regions of the lungs. Selonsertib also suppressed the IgE levels in serum and the protein levels of IL-13 in the bronchoalveolar lavage fluid. These results suggest that selonsertib may ameliorate allergic asthma by suppressing immune responses and be applicable to allergic asthma.
Background: While asthma control is defined as the extent to which the various manifestations of asthma are reduced by treatment, current guidelines of asthma recommend assessment of asthma control without consideration of airway inflammation. Our aim was to investigate the relationships between fractional exhaled nitric oxide (FeNO), a reliable marker of airway inflammation, and levels of asthma control in patients treated with inhaled corticosteroids (ICS). Methods: We enrolled 71 adult patients with asthma who had been treated with ICS for more than four months. FeNO was measured and spirometry was performed at the time of enrollment. Asthma control was assessed (a) by the physician based on the Global Initiative for Asthma guidelines, (b) by the patients, and (c) by using the Asthma Control Test (ACT). Statistical analyses were done to analyze the relationships between (i) FeNO and (ii) measures of asthma control and clinical indices for asthma manifestations. Results: There was no significant difference in FeNO levels between the three groups according to levels of asthma control (controlled, partly controlled and uncontrolled) as determined by the physician (p=0.81), or by the patients (p=0.81). In addition, FeNO values were not significantly correlated with the ACT scores (r=0.031, p=0.807), while FeNO showed a correlation with peripheral blood eosinophil counts (p<0.001). Conclusion: These findings demonstrate that FeNO levels are not associated with measures of asthma control in patients treated with ICS. Information on airway inflammation from FeNO concentrations seems to be unrelated to levels of asthma control
Inhaled corticosteroids (ICSs) have been widely used as a key medication for asthma control. However, ICSs have been known to cause respiratory infections, such as pneumonia and pulmonary tuberculosis. Consequently, a dilemma exists regarding recommendation of persistent lifetime use of ICSs to mild asthma patients. Short-acting ${\beta}$-agonists (SABAs) have also been widely used for symptom relief. However, SABAs have been reported to increase the risk of asthma-related death, though incidences have been very rare. Consequently, a dilemma exists regarding recommendation of a SABA alone without an ICS or a controller to asthma patients even with very mild disease. In the real world, asthma patients tend to intermittently use ICS and more likely to be dependent on SABA since many patients want immediate relief of their symptoms. Consequently, a dilemma exists regarding the underuse of ICSs but the overuse of SABAs. One strategy for solving the presented dilemma would be identification of patients with asthma who require persistent use of asthma controllers. Such patients, who may be referred to as "persistent controller users," should continuously receive ICSs, even under controlled states of asthma. Another strategy would be a patient-adjusted, symptom-driven, intermittent-to-regular treatment combining low-dose ICS/rapid-onset long-acting ${\beta}$-agonists instead of using a SABA alone or with low-dose ICS for the asthma patients with mild disease. Both of these two strategies could avoid the risky treatment of a SABA alone without an ICS and could reduce the dose of ICS with the maintenance of asthma control.
Lee, Song Han;Lee, Koh Woon;Hwang, Yoon Ha;Odajima, Hiroshi
Kosin Medical Journal
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v.33
no.2
/
pp.171-180
/
2018
Objectives: We investigated whether asthma attacks in asthmatic children were caused by short-term exposure to particulate $matter(PM)_{2.5}$. Methods: Subjects were 411 patients who received inhalation therapy in National Fukuoka Hospital, from March to May 2013. All subjects were outpatients. We surveyed the air quality measurement results in the stations closest to the address of the patients. Data were used from the City of Fukuoka website data on air pollution. We carried out a case-crossover study and compared $PM_{2.5}$ concentration between 7 days after asthma attack occurred and the day asthma attack occurred and 1, 2 and 3 days before asthma attack occurred. Results: Highest hourly concentration of the day (OR 1.013, 95%CI 1.000-1.025) showed a significant association with 1 day before $PM_{2.5}$ concentration statistically. And 0-1 year-old infants were more vulnerable to the highest concentration of 1 day before $PM_{2.5}$ concentration(P < 0.05). Average concentration of $NO_2$ and $O_3$ and asthma attack also showed a significant association. Conclusions: Maximal daily $PM_{2.5}$ concentrations within 24 hours prior to the attack affect asthma exacerbation. 0-1 year-old infants are particularly vulnerable to $PM_{2.5}$ concentration. Asthma exacerbation is aggravated by $NO_2$ and $O_3$ concentration on the day of the asthma attack.
Journal of The Korean Society of Integrative Medicine
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v.9
no.3
/
pp.47-58
/
2021
Purpose : This study aimed to investigate the association between asthma and oral health and factors influencing asthma in adults. We also investigated whether asthma is related to mental health and physiological factors of blood. Methods : Data from 12,639 adults was taken from the 7th period (2016~2018) Korea National Health and Nutrition Examination Survey and analyzed using with SPSS 22.0 statistical program. Statistical analysis of data included frequency analysis, cross-analysis, and logistic regression analysis. For continuous data, an independent sample t-test was performed. The statistical significance level was defined as 0.05. Results : The probability of asthma occurrence was statistically different within general characteristics (gender, age, school grade, income, and drinking). By independent variables in a logistic regression analysis, the asthma diagnosis group had more people with speech discomfort (OR=1.37), chewing discomfort (OR=1.29), and oral pain (OR=.73). We found that people with asthma had a more unfavorable perception of their health (OR=1.73), suffered more depression (OR=.45), stress (OR=.66), and limited activity (OR=2.38). Moreover, the white blood cell count (OR=1.10) and high sensitivity C-reactive protein test (OR=1.06) also showed higher values than the control group. Conclusion : Our study showed that oral health and mental health were associated with the asthma, and influencing factors were oral health and behavior and mental health-related characteristics. Therefore, it is necessary to understand asthma-related risk factors for oral health and recognize the importance of systematic oral care education and regular dental visits for patients receiving asthma treatment. Thus, this study provides valuable insights on appropriate oral health management and prevention of asthma in patients.
BACKGROUND/OBJECTIVES: Asthma and allergic rhinitis (AR) are closely related and considered as allergic respiratory diseases (ARD), and their prevalence has recently increased. Data on the association of dietary antioxidant vitamin intake with asthma and AR in adults are limited. The present study aimed to investigate the associations of vitamin A and C intake with asthma, AR, and all cases of both diseases in young adults who participated in a cross-sectional national survey, with the use of high-sensitivity C-reactive protein (hs-CRP) level as an effect modifier. SUBJECTS/METHODS: This study included 6,293 male and female adults aged 20-49 years from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted between 2016 and 2018. The questionnaire-based reports on asthma and AR diagnosis were used to determine outcome variables. Further, 24-h recall data on dietary vitamin A and C, carotene, and retinol intake were acquired. Logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence interval (CI). RESULTS: Dietary vitamin C intake was inversely associated with asthma prevalence among participants with hs-CRP levels (≥ 1 mg/L); the OR of asthma prevalence was 0.27 (95% CI, 0.08-0.84) for participants with vitamin C consumption ≥ 75 mg/day compared with those consuming < 20 mg/day. Similar association analyses limiting to non-users of dietary supplements were performed to rule out the potential effects of supplement intake on the outcomes; results showed a stronger association. However, the association between vitamin C and asthma was not significant in participants with hs-CRP levels < 1 mg/L; the OR of asthma was 1.44 (95% CI, 0.66-3.16) for participants with vitamin C consumption ≥ 75 mg/day compared with those consuming < 20 mg/day. Vitamin C intake was not associated with AR. Moreover, there was no association between vitamin A intake and neither asthma nor AR. CONCLUSIONS: These findings suggest that higher vitamin C intake may play a potential role in reducing asthma prevalence. Nevertheless, further studies should be conducted to evaluate whether this association is causal.
Background/Aims: Despite short-acting β2-agonist (SABA) overuse being associated with poor asthma outcomes, data on SABA use in South Korea is scarce. Herein, we describe prescription patterns of SABA and other asthma medications in patients from the South Korean cohort of the SABA use IN Asthma (SABINA) III study. Methods: This study included patients with asthma aged ≥ 12 years, who had ≥ 3 consultations with the same healthcare provider, and medical records containing data for ≥ 12 months prior to the study visit. Patients were classified by investigator-defined asthma severity (per 2017 Global Initiative for Asthma recommendations) and practice type (primary or specialist care). Data on disease characteristics, asthma treatments, and clinical outcomes in the 12 months before the study visit were collected using electronic case report forms. Results: Data from 476 patients (mean age, 55.4 years; female, 63.0%) were analyzed. Most patients were treated by specialists (83.7%) and had moderate-to-severe asthma (91.0%). Overall, 7.6% of patients were prescribed ≥ 3 SABA canisters (defined as over-prescription). In patients prescribed SABA in addition to maintenance therapy, 47.4% were over-prescribed SABA. Most patients (95.4%) were prescribed a fixed-dose combination of an inhaled corticosteroid and a long-acting β2-agonist as maintenance therapy. Although asthma was well-controlled/partly-controlled in 91.6% of patients, 29.6% experienced ≥ 1 severe asthma exacerbation. Conclusions: SABA over-prescription was reported in nearly 50% of patients prescribed SABA in addition to maintenance therapy, underscoring the need to align clinical practices with the latest evidence-based recommendations and educate physicians and patients on appropriate SABA use.
Asthma comprises a heterogeneous group of disorders characterized by airway inflammation, airway obstruction, and airway hyperresponsiveness (AHR). Airway inflammation, which induces AHR and recurrence of asthma, is the main pathophysiology of asthma. The fractional exhaled nitric oxide (FeNO) level is a noninvasive, reproducible measurement of eosinophilic airway inflammation that is easy to perform in young children. As airway inflammation precedes asthma attacks and airway obstruction, elevated FeNO levels may be useful as predictive markers for risk of recurrence of asthma. This review discusses FeNO measurements among early-childhood wheezing phenotypes that have been identified in large-scale longitudinal studies. These wheezing phenotypes are classified into three to six categories based on the onset and persistence of wheezing from birth to later childhood. Each phenotype has characteristic findings for atopic sensitization, lung function, AHR, or FeNO. For example, in one birth cohort study, children with asthma and persistent wheezing at 7 years had higher FeNO levels at 4 years compared to children without wheezing, which suggested that FeNO could be a predictive marker for later development of asthma. Preschool-aged children with recurrent wheezing and stringent asthma predictive indices also had higher FeNO levels in the first 4 years of life compared to children with wheezing and loose indices or children with no wheeze, suggesting that FeNO measurements may provide an additional parameter for predicting persistent wheezing in preschool children. Additional large-scale longitudinal studies are required to establish cutoff levels for FeNO as a risk factor for persistent asthma.
Woo, Yeonduk;Jeong, Dongjin;Chung, Doo Hyun;Kim, Hye Young
IMMUNE NETWORK
/
v.14
no.4
/
pp.171-181
/
2014
Asthma is a common pulmonary disease with several different forms. The most studied form of asthma is the allergic form, which is mainly related to the function of Th2 cells and their production of cytokines (IL-4, IL-5, and IL-13) in association with allergen sensitization and adaptive immunity. Recently, there have been many advances in understanding non-allergic asthma, which seems to be related to environmental factors such as air pollution, infection, or even obesity. Cells of the innate immune system, including macrophages, neutrophils, and natural killer T cells as well as the newly described innate lymphoid cells, are effective producers of a variety of cytokines and seem to play important roles in the development of non-allergic asthma. In this review, we focus on recent findings regarding innate lymphoid cells and their roles in asthma.
Asthma is a chronic inflammation of the airway associated with increased bronchial hyperresponsiveness that leads to recurrent episodes of cough, wheezing, breathless, chest tightness. According the recent studies, repeated airway inflammation leads to structural changes so called 'airway remodeling' and associated with decreased pulmonary function. Airway remodeling begins form the early stage of asthma and the early diagnosis and management is very important to prevent airway remodeling. Medication for asthma can be classified into acute symptom reliever and chronic controller. Short acting beta2 agonist is a well-known reliever that reduced asthma symptoms within minutes. Controllers should be taken daily as a long-term basis to control airway inflammation. Inhaled corticosteroid(ICS) is the most effective controller in current use. However, in some patients ICS monotherapy is not sufficient to control asthma. In those cases, other medications such as long acting beta2 agonist, leukotriene modifier or sustained-release theophylline should be added to ICS, which called Add-on-Therapy. Combination inhaler devices are easy to use. Oral leukotriene modifier has a good compliance especially in children. Finally, as asthma is a chronic disease, the development of on-going partnership among health care professionals, the patients, and the patients' family is necessary for the effective management of asthma.
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