• IMMUNE NETWORK
• /
• v.19 no.1
• /
• pp.5.1-5.12
• /
• 2019

Autophagy is a homeostatic mechanism that discards not only invading pathogens but also damaged organelles and denatured proteins via lysosomal degradation. Increasing evidence suggests a role for autophagy in inflammatory diseases, including infectious diseases, Crohn's disease, cystic fibrosis, and pulmonary hypertension. These studies suggest that modulating autophagy could be a novel therapeutic option for inflammatory diseases. Eosinophils are a major type of inflammatory cell that aggravates airway inflammatory diseases, particularly corticosteroid-resistant inflammation. The eosinophil count is a useful tool for assessing which patients may benefit from inhaled corticosteroid therapy. Recent studies demonstrate that autophagy plays a role in eosinophilic airway inflammatory diseases by promoting airway remodeling and loss of function. Genetic variant in the autophagy gene ATG5 is associated with asthma pathogenesis, and autophagy regulates apoptotic pathways in epithelial cells in individuals with chronic obstructive pulmonary disease. Moreover, autophagy dysfunction leads to severe inflammation, especially eosinophilic inflammation, in chronic rhinosinusitis. However, the mechanism underlying autophagy-mediated regulation of eosinophilic airway inflammation remains unclear. The aim of this review is to provide a general overview of the role of autophagy in eosinophilic airway inflammation. We also suggest that autophagy may be a new therapeutic target for airway inflammation, including that mediated by eosinophils.

• Tuberculosis and Respiratory Diseases
• /
• v.81 no.1
• /
• pp.73-79
• /
• 2018

Background: Osteoporosis is a common disease that occurs comorbidly in patients with chronic inflammatory airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap syndrome (ACOS). However, the prevalence of osteoporosis in patients with ACOS has not widely been evaluated. Therefore, we investigated the prevalence of osteoporosis and its relationship with the clinical parameters of patients with asthma, COPD, and ACOS. Methods: This was a retrospective, cross-sectional study. Bone mineral density (BMD), lung function tests, and disease status evaluations were conducted. Results: A total of 321 patients were enrolled: 138 with asthma, 46 with ACOS, and 137 with COPD. One hundred and ninety-three patients (60.1%) were diagnosed with osteoporosis (53.6% of asthma, 65.2% of ACOS, and 65.0% of COPD). Patients with ACOS showed a significantly lower BMD and T-score than did those with asthma. In addition to age, sex, and body mass index (BMI), which were previously reported to be associated with BMD, BMD also had a negative correlation with the diagnosis of ACOS, as compared to a diagnosis of asthma, after adjusting for age, sex, BMI, smoking, and inhaled corticosteroid use (p=0.001). Among those patients with COPD and ACOS, BMD was negatively associated with the COPD Assessment Test (CAT) after adjustment (p<0.001). Inhaled corticosteroid was not associated with the prevalence of osteoporosis and BMD. Conclusion: Patients with ACOS, particularly aged and lean women, should be more carefully monitored for osteoporosis as compared to patients with asthma.

• Clinical and Experimental Pediatrics
• /
• v.55 no.9
• /
• pp.330-336
• /
• 2012

Purpose: Fractional exhaled nitric oxide (FeNO) and forced expiratory flow between 25% and 75% of vital capacity ($FEF_{25-75}$) are not included in routine monitoring of asthma control. We observed changes in FeNO level and $FEF_{25-75}$ after FeNO-based treatment with inhaled corticosteroid (ICS) in children with controlled asthma (CA). Methods: We recruited 148 children with asthma (age, 8 to 16 years) who had maintained asthma control and normal forced expiratory volume in the first second ($FEV_1$) without control medication for ${\geq}3$ months. Patients with FeNO levels >25 ppb were allocated to the ICS-treated (FeNO-based management) or untreated group (guideline-based management). Changes in spirometric values and FeNO levels from baseline were evaluated after 6 weeks. Results: Ninety-three patients had FeNO levels >25 ppb. These patients had lower $FEF_{25-75}$ % predicted values than those with FeNO levels ${\leq}25$ ppb (P<0.01). After 6 weeks, the geometric mean (GM) FeNO level in the ICS-treated group was 45% lower than the baseline value, and the mean percent increase in $FEF_{25-75}$ was 18.7% which was greater than that in other spirometric values. There was a negative correlation between percent changes in $FEF_{25-75}$ and FeNO (r=-0.368, P=0.001). In contrast, the GM FeNO and spirometric values were not significantly different from the baseline values in the untreated group. Conclusion: The anti-inflammatory treatment simultaneously improved the FeNO levels and $FEF_{25-75}$ in CA patients when their FeNO levels were >25 ppb.

• Korean Journal of Clinical Pharmacy
• /
• v.26 no.4
• /
• pp.298-305
• /
• 2016

Background: This study is to investigate the prescription patterns and factors related to the number of medications treating chronic obstructive pulmonary disease (COPD) in patients under 65 years old according to GOLD guidelines. Methods: We retrospectively analyzed the medical records of patients aged 40-64 years with a diagnosis of COPD from January to March 2016. Patients were classified by combined assessment of COPD (grades A, B, C, D) using spirometry, exacerbation history, mMRC, and/or CAT results. We analyzed prescribed medications, treatment options and factors related to the numbers of COPD medications. Results: The total number of prescriptions were 251. About 35.5% of patients were classified as GOLD A, 34.2% as GOLD B, 17.1% as GOLD C and 13.2% as GOLD D. Inhaled bronchodilator was prescribed for 86.9% of patients and the most frequent COPD medication was long-acting muscarinic antagonist (LAMA) followed by inhaled corticosteroids/long acting beta agonist (ICS/LABA). The majority of low risk patients (GOLD A/B) were prescribed a monotherapy with LAMA or LABA. For high risk patients (GOLD C/D), combination treatment with ICS+LAMA+LABA was mostly prescribed. The 21.2% of patients in GOLD D received systemic corticosteroid. The average number of medications per prescription was 3.7, and this number increased with increasing COPD grade, COPD duration and lung function reduction ($FEV_1$, $FEV_1/FVC$). Conclusion: Generally high adherence to GOLD guideline recommendations was reported. Given the progressive nature of the disease, results suggest that closer attention to respiratory symptoms for early detection, diagnosis, and appropriate treatment of COPD is warranted.

• Tuberculosis and Respiratory Diseases
• /
• v.85 no.3
• /
• pp.227-236
• /
• 2022

Background: The use of low-dose inhaled corticosteroid-formoterol as reliever monotherapy has recently been recommended in the asthma treatment guidelines. However, the efficacy of this treatment strategy has not yet been determined during the stepping-down period in moderate asthma. This study aimed to evaluate the feasibility of reducing treatment to as-needed budesonide-formoterol (BFM) in moderate asthma with complete remission. Methods: We randomly assigned 31 patients (8 males and 23 females with a mean age of 57.2 years) with complete remission of asthma by inhaled BFM (160/4.5 ㎍) twice daily to receive BFM (160/4.5 ㎍) as needed (16 patients), or budesonide (BUD) (200 ㎍) twice daily (15 patients). The study was an open-label study done for 48 weeks, with the primary outcome as the cumulative percentages of patients with treatment failure (asthma exacerbation or loss of asthma control or lack of satisfaction after using medications) in the two groups. Results: Six patients (42%) using as-needed BFM had treatment failure, as compared with three patients (21.4%) using BUD maintenance (hazards ratio for as-needed BFM, 1.77; 95% confidential interval, 0.44-7.12; p=0.41). The changes in forced expiratory volume in 1 second were -211.3 mL with as-needed BFM versus -97.8 mL with BUD maintenance (difference, 113.5 mL; p=0.75) and the change in fractional exhaled nitric oxide was significantly higher in both groups, at 8.68 parts per billion (ppb) in the as-needed BFM group and 2.5 ppb. in the BUD maintenance group (difference, 6.18 ppb; p=0.049). Conclusion: Compared with BUD maintenance, there were no significant differences in treatment failure rate in patients who received as-needed BFM during the stepping down period in moderate asthma. However, they showed reduced lung function and relapsed airway inflammation. The results are limited by imprecision, and further large RCTs are needed.

• Tuberculosis and Respiratory Diseases
• /
• v.51 no.1
• /
• pp.25-34
• /
• 2001

Background : Inhaled glucocorticoids are the medical treatment of choice in asthma patients. Fluticasone propionate is one of the most effective inhaled corticosteroids and has been reported to have minimal effect on the hypothalamic-pituitary-adrenal axis at the recommended dose. However, reports of long-term trials characterizing their systemic safety with chronic use are rare. This study was designed to evaluate the long-term safety of inhaled fluticasone propionate to the hypothalamic-pituitary-adrenal axis. Method : This study was conducted on 21 patients to evaluate the adrenal response to rapid ACTH stimulation test after 6 months of treatment with fluticasone propionate from $200\;{\mu}g$ to $750\;{\mu}g$ daily. The serum cortisol levels was measured to assess its effect on the hypothalamic-pituitary-adrenal axis just prior to the injection, at 30 minutes and 60 minutes after an intramuscular injection of synthetic ACTH. Result : The mean dose of inhaled fluticasone propionate was $355\;{\mu}g$ per day(SD=$174\;{\mu}g$, range=$200\;{\mu}g$ to $750\;{\mu}g$). The mean serum cortisol levels of the patients was $11.0\;{\mu}g/d{\ell}$(SD=$6.4\;{\mu}g/d{\ell}$) prior to the injection, $20.0\;{\mu}g/d{\ell}$ (SD=$7.7\;{\mu}g/d{\ell}$) after 30 minutes, and $23.0\;{\mu}g/d{\ell}$(SD=$6.3\;{\mu}g/d{\ell}$) after 60 minutes. Sixteen patients of the 21 patients had a normal response(> $18\;{\mu}g/d{\ell}$), and 5 out of the 21 patients had serum cortisol levels below the normal range after the rapid ACTH stimulation test. Conclusion: Adrenal suppression occurred in 5 out of 21 patients with 6 months treatment with inhaled fluticasone propionate.

• Clinical and Experimental Pediatrics
• /
• v.49 no.6
• /
• pp.581-588
• /
• 2006

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.

• Korean Journal of Clinical Pharmacy
• /
• v.27 no.2
• /
• pp.113-118
• /
• 2017

Objective: International institutes such as Global institute for Asthma(GINA), KAAACI(Republic of Korea), NHLBI(USA), BTS(UK) and JSA(Japan) have published guidelines for asthma treatment. The aim of this study was to compare the representatives' international guidelines of pharmacotherapy for pediatric asthma. Methods: The recommendations related to pharmacotherapy for pediatric asthma were extracted from the latest representatives' international guidelines, and comprehensive comparisons were conducted. Results: Major comparison outcomes between international guidelines were evaluated as follows: classification system on severity and pediatric age group, recommendation for inhaled corticosteroid dose, recommendation for pediatric age group of theophylline in mild asthma, and recommendation for pediatric age group of tiotropium in severe asthma. Clinical trials emphasized the adverse effects of theophylline, whereas tiotropium demonstrated beneficial actions for pediatric asthma. Therefore, theophylline was recommended for older patients with persistent asthma, and tiotropium was considered to be suitable for younger patients with severe asthma according to GINA guidelines. Conclusion: These findings address the requirement to harmonize international guidelines of pharmacotherapy in pediatric asthma. In addition, the findings suggest that KAAACI needs to update its pharmacotherapy guidelines of theophylline, tiotropium and other medicines recently approved.

• Tuberculosis and Respiratory Diseases
• /
• v.76 no.3
• /
• pp.105-113
• /
• 2014

From January 2012 up until March 2013, many articles with huge clinical importance in asthma were published based on large numbered clinical trials or meta-analysis. The main subjects of these studies were the new therapeutic plan based on the asthma phenotype or efficacy along with the safety issues regarding the current treatment guidelines. For efficacy and safety issues, inhaled corticosteroid tapering strategy or continued long-acting beta agonists use was the major concern. As new therapeutic trials, monoclonal antibodies or macrolide antibiotics based on inflammatory phenotypes have been under investigation, with promising preliminary results. There were other issues on the disease susceptibility or genetic background of asthma, particularly for the "severe asthma" phenotype. In the era of genome and pharmacogenetics, there have been extensive studies to identify susceptible candidate genes based on the results of genome wide association studies (GWAS). However, for severe asthma, which is where most of the mortality or medical costs develop, it is very unclear. Moreover, there have been some efforts to find important genetic information in order to predict the possible disease progression, but with few significant results up until now. In conclusion, there are new on-going aspects in the phenotypic classification of asthma and therapeutic strategy according to the phenotypic variations. With more pharmacogenomic information and clear identification of the "severe asthma" group even before disease progression from GWAS data, more adequate and individualized therapeutic strategy could be realized in the future.

• Tuberculosis and Respiratory Diseases
• /
• v.71 no.2
• /
• pp.106-113
• /
• 2011

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