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1.
Article in English | WPRIM | ID: wpr-903682

ABSTRACT

Background/Aims@#Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a major regulator of Wnt signaling, which is involved in fibroblast dysfunction. Because its role has not been evaluated in idiopathic pulmonary fibrosis (IPF), we examined the clinical implications of ROR2 expression. @*Methods@#ROR2 mRNA expression was measured using reverse transcription polymerase chain reaction in lung tissue-derived fibroblasts from IPF patients (n = 14) and from controls (n = 10). ROR2 protein was measured using enzyme-linked immunosorbent assay in primary fibroblasts from IPF patients (n = 14) and controls (n = 10), and in bronchoalveolar lavage (BAL) fluids obtained from normal controls (NC; n = 30). IPF patients (n = 84), and other patients with interstitial lung diseases, including nonspecific interstitial pneumonia (NSIP; n = 10), hypersensitivity pneumonitis (HP; n = 10), and sarcoidosis (n = 10). @*Results@#ROR2 mRNA and protein levels were significantly higher in IPF fibroblasts than in controls (p = 0.003, p = 0.0017, respectively). ROR2 protein levels in BAL fluids from patients with IPF were significantly higher than in those from NC (p < 0.001), and from patients with NSIP (p = 0.006), HP (p = 0.004), or sarcoidosis (p = 0.004). Receiver operating characteristic curves showed a clear difference between IPF and NC in ROR2 protein level (area under the curve, 0.890; confidence interval, 0.829 to 0.950; p < 0.001). ROR2 protein levels were significantly higher in GAP stage III than in GAP stages I and II (p = 0.016). @*Conclusions@#ROR2 may be related to the development of IPF, and its protein level may be a useful and severity-dependent candidate marker for IPF.

2.
Article in English | WPRIM | ID: wpr-903670

ABSTRACT

Background/Aims@#Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. @*Methods@#This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. @*Results@#Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). @*Conclusions@#Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.

3.
Article in English | WPRIM | ID: wpr-875477

ABSTRACT

Background/Aims@#The efficacy and safety of mepolizumab in patients with severe eosinophilic asthma has been evaluated in a global clinical trial programme. This post hoc analysis assesses the efficacy and safety of mepolizumab in Korean patients. @*Methods@#Data from Korean patients in the Phase III, placebo-controlled, randomised DREAM (MEA112997/NCT01000506) and MENSA (MEA115588/ NCT01691521) studies were included. Patients ≥ 12 years old with severe eosinophilic asthma received mepolizumab (DREAM: 75, 250 or 750 mg intravenously [IV]; MENSA: 75 mg IV or 100 mg subcutaneously [SC]), or placebo every 4 weeks for 52 weeks (DREAM) or 32 weeks (MENSA). The primary outcome was the rate of clinically significant asthma exacerbations. Secondary outcomes included forced expiratory volume in 1 second (FEV1), Asthma Control Questionnaire (ACQ) and St George’s Respiratory Questionnaire (SGRQ) scores (MENSA only). Blood eosinophil counts (BEC) and safety were assessed throughout. @*Results@#Reductions in the rate of clinically significant asthma exacerbations were observed with the approved (100 mg SC) and bioequivalent (75 mg IV) doses of mepolizumab in Korean patients who participated in DREAM and MENSA. In MENSA, trends for improvements from baseline at week 32 in pre-bronchodilator FEV1 (75 mg IV group), ACQ-5 and SGRQ scores (in both treatment groups) were seen versus placebo in Korean patients. Incidence of on-treatment adverse events was similar in Korean patients versus non-Korean patients as were observed reductions from baseline in BEC. @*Conclusions@#Mepolizumab treatment provided clinical benefits for Korean patients with severe eosinophilic asthma; the safety profile is consistent with the overall population.

4.
Article in English | WPRIM | ID: wpr-895978

ABSTRACT

Background/Aims@#Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a major regulator of Wnt signaling, which is involved in fibroblast dysfunction. Because its role has not been evaluated in idiopathic pulmonary fibrosis (IPF), we examined the clinical implications of ROR2 expression. @*Methods@#ROR2 mRNA expression was measured using reverse transcription polymerase chain reaction in lung tissue-derived fibroblasts from IPF patients (n = 14) and from controls (n = 10). ROR2 protein was measured using enzyme-linked immunosorbent assay in primary fibroblasts from IPF patients (n = 14) and controls (n = 10), and in bronchoalveolar lavage (BAL) fluids obtained from normal controls (NC; n = 30). IPF patients (n = 84), and other patients with interstitial lung diseases, including nonspecific interstitial pneumonia (NSIP; n = 10), hypersensitivity pneumonitis (HP; n = 10), and sarcoidosis (n = 10). @*Results@#ROR2 mRNA and protein levels were significantly higher in IPF fibroblasts than in controls (p = 0.003, p = 0.0017, respectively). ROR2 protein levels in BAL fluids from patients with IPF were significantly higher than in those from NC (p < 0.001), and from patients with NSIP (p = 0.006), HP (p = 0.004), or sarcoidosis (p = 0.004). Receiver operating characteristic curves showed a clear difference between IPF and NC in ROR2 protein level (area under the curve, 0.890; confidence interval, 0.829 to 0.950; p < 0.001). ROR2 protein levels were significantly higher in GAP stage III than in GAP stages I and II (p = 0.016). @*Conclusions@#ROR2 may be related to the development of IPF, and its protein level may be a useful and severity-dependent candidate marker for IPF.

5.
Article in English | WPRIM | ID: wpr-895966

ABSTRACT

Background/Aims@#Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. @*Methods@#This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. @*Results@#Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). @*Conclusions@#Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.

7.
Article in English | WPRIM | ID: wpr-904148

ABSTRACT

For the past three decades, more than a thousand of genetic studies have been performed to find out the genetic variants responsible for the risk of asthma. Until now, all of the discovered single nucleotide polymorphisms have explained genetic effects less than initially expected. Thus, clarification of environmental factors has been brought up to overcome the ‘missing’ heritability. The most exciting solution is epigenesis because it intervenes at the junction between the genome and the environment. Epigenesis is an alteration of genetic expression without changes of DNA sequence caused by environmental factors such as nutrients, allergens, cigarette smoke, air pollutants, use of drugs and infectious agents during pre- and post-natal periods and even in adulthood. Three major forms of epigenesis are composed of DNA methylation, histone modifications, and specific microRNA. Recently, several studies have been published on epigenesis in asthma and allergy as a powerful tool for research of genetic heritability in asthma albeit epigenetic changes are at the starting point to obtain the data on specific phenotypes of asthma. In this presentation, we mainly review the potential role of DNA CpG methylation in the risk of asthma and its sub-phenotypes including nonsteroidal anti-inflammatory exacerbated respiratory diseases.

8.
Article in English | WPRIM | ID: wpr-811069

ABSTRACT

PURPOSE: Different characteristics of airway microbiome in asthmatics may lead to differential immune responses, which in turn cause eosinophilic or neutrophilic airway inflammation. However, the relationships among these factors have yet to be fully elucidated.METHODS: Microbes in induced sputum samples were subjected to sequence analysis of 16S rRNA. Airway inflammatory phenotypes were defined as neutrophils (>60%) and eosinophils (>3%), and inflammation endotypes were defined by levels of T helper (Th) 1 (interferon-γ), Th2 (interleukin [IL]-5 and IL-13), Th-17 (IL-17), and innate Th2 (IL-25, IL-33, and thymic stromal lymphopoietin) cytokines, inflammasomes (IL-1β), epithelial activation markers (granulocyte-macrophage colony-stimulating factor and IL-8), and Inflammation (IL-6 and tumor necrosis factor-α) cytokines in sputum supernatants was assessed by enzyme-linked immunosorbent assay.RESULTS: The numbers of operational taxonomic units were significantly higher in the mixed (n = 21) and neutrophilic (n = 23) inflammation groups than in the paucigranulocytic inflammation group (n = 19; p < 0.05). At the species level, Granulicatella adiacens, Streptococcus parasanguinis, Streptococcus pneumoniae, Veillonella rogosae, Haemophilus parainfluenzae, and Neisseria perflava levels were significantly higher in the eosinophilic inflammation group (n = 20), whereas JYGU_s levels were significantly higher in the neutrophilic inflammation group compared to the other subtypes (P < 0.05). Additionally, IL-5 and IL-13 concentrations were correlated with the percentage of eosinophils (P < 0.05) and IL-13 levels were positively correlated with the read counts of Porphyromonas pasteri and V. rogosae (P < 0.05). IL-1β concentrations were correlated with the percentage of neutrophils (P < 0.05). had a tendency to be positively correlated with the read count of JYGU_s (P = 0.095), and was negatively correlated with that of S. pneumoniae (P < 0.05).CONCLUSIONS: Difference of microbial patterns in airways may induce distinctive endotypes of asthma, which is responsible for the neutrophilic or eosinophilic inflammation in asthma.


Subject(s)
Asthma , Colony-Stimulating Factors , Cytokines , Enzyme-Linked Immunosorbent Assay , Eosinophils , Haemophilus parainfluenzae , Inflammasomes , Inflammation , Interleukin-13 , Interleukin-33 , Interleukin-5 , Microbiota , Necrosis , Neisseria , Neutrophils , Phenotype , Pneumonia , Porphyromonas , Sequence Analysis , Sputum , Streptococcus , Streptococcus pneumoniae , Veillonella
9.
Article in English | WPRIM | ID: wpr-811067

ABSTRACT

PURPOSE: Asthma in the elderly (EA; ≥ 65 years of age) is increasing, adding a heavy socioeconomic burden to the healthcare system. However, little is known about risk factors associated with acute exacerbations in EA patients. The objective of this study was to investigate risk factors for acute exacerbation in EA compared to non-elderly asthma (NEA).METHODS: We combined data from 3 adult asthma cohorts under a unified protocol and database. Asthmatic patients with regular follow-up during a 1-year period were selected from the cohorts to identify the risk factors predicting acute exacerbations in EA compared to NEA.RESULTS: We selected a total of 1,086 patients from the merged cohort. During the observation period, 503 and 583 patients were assigned to the EA and NEA groups, respectively. The exacerbation rate was 31.0% in the EA and 33.2% in the NEA group. Multivariate logistic regression analysis revealed fixed airway obstruction, chronic rhinosinusitis (CRS), and male sex as independent risk factors for exacerbation in the EA group. In the NEA group, exacerbation increased along with an increase in eosinophil count. Bayesian analysis of the interactions among clinical factors revealed that forced expiratory volume in 1 second/forced vital capacity was directly related to exacerbation in the EA group, and eosinophil count was related to exacerbation in the NEA group.CONCLUSIONS: We suggest that fixed airway obstruction and CRS as the important clinical factors predicting acute exacerbations in EA, whereas in NEA, eosinophil count was the strong predictor of exacerbation.


Subject(s)
Adult , Aged , Airway Obstruction , Asthma , Bayes Theorem , Cohort Studies , Delivery of Health Care , Eosinophils , Follow-Up Studies , Forced Expiratory Volume , Humans , Logistic Models , Male , Risk Factors , Vital Capacity
10.
Article | WPRIM | ID: wpr-831541

ABSTRACT

Background@#Exposure to ozone (O3) induces neutrophilic inflammation and goblet cell hyperplasia in humans and experimental animals. Because the solute carrier family 26-member 4 (Slc26a4; pendrin) gene induces mucin production and intraluminal acidification in the airways, it was hypothesized to be a key molecule in O3-induced airway injury. Thus, we evaluated the role of Slc26a4 and the protective effects of ammonium chloride (NH4Cl) in O3 -induced airway injury in mice. @*Methods@#Six-week-old female BALB/c mice were exposed to filtered air or O3 for 21 days (2 ppm for 3 hr/day). NH4Cl (0, 0.1, 1, and 10 mM) was administered intratracheally into the airways. Airway resistance was measured using a flexiVent system, and bronchoalveolar lavage fluid (BALF) cells were differentially counted. Slc26a4 and Muc5ac proteins and mRNA were measured via western blotting, real-time polymerase chain reaction, and immunostaining. Tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-17, IL-1β, and caspase-1 were analyzed via western blotting. @*Results@#The levels Slc26a4 protein and mRNA significantly increased in lung tissues from Day 7 to Day 21 of O3exposure, with concomitant increases in lung resistance, numbers of goblet cells in lung tissues, and inflammatory cells and thiocyanate (SCN− ) levels in BALF in a time-dependent manner. Treatment with NH4Cl significantly reduced these changes to levels similar to those of sham-treated mice, with a concomitant reduction of Slc26a4 proteins in lung lysates and SCN − levels in BALF. Slc26a4 protein was co-expressed with muc5ac protein in the bronchial epithelium, as indicated by immunofluorescence staining. NH4 Cl treatment also significantly attenuated the O3 -induced increases in IFN-γ, TNF-α, IL-17, IL-1β, and p20-activated caspase-1. @*Conclusion@#Slc26a4 may be involved in O3 -induced inflammatory and epithelial changes in the airways via activation of the inflammasome and the induction of IL-17 and IFN-γ. NH4 Cl shows a potential as a therapeutic agent for controlling O3 -induced airway inflammation and epithelial damage by modulating Slc26a4 expression.

11.
Article in English | WPRIM | ID: wpr-896607

ABSTRACT

Purpose@#Cold air is a major environmental factor that exacerbates asthma. Transient receptor potential melastatin family member 8 (TRPM8) is a cold-sensing channel expressed in the airway epithelium. However, its role in airway inflammation remains unknown. We investigated the role of TRPM8 in innate immune responses in bronchial epithelial cells and asthmatic subjects. @*Methods@#The TRPM8 mRNA and protein expression on BEAS2B human bronchial epithelial cells was examined by real-time polymerase chain reaction (PCR), immunofluorescence staining and western blotting. Additionally, interleukin (IL)-4, IL-6, IL-8, IL-13, IL-25 and thymic stromal lymphopoietin (TSLP) levels before and after menthol, dexamethasone and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) treatments were measured via real-time PCR. TRPM8 protein levels in the supernatants of induced sputum from asthmatic subjects and normal control subjects were measured using enzyme-linked immunosorbent assay, and mRNA levels in sputum cell lysates were measured using real-time PCR. @*Results@#Treatment with up to 2 mM menthol dose-dependently increased TRPM8 mRNA and protein in BEAS2B cells compared to untreated cells (P < 0.001) and concomitantly increased IL-25 and TSLP mRNA (P < 0.05), but not IL-33 mRNA. BCTC (10 μM) significantly abolished menthol-induced up-regulation of TRPM8 mRNA and protein and IL-25 and TSLP mRNA (P < 0.01). TRPM8 protein levels were higher in the supernatants of induced sputum from asthmatic subjects (n = 107) than in those from healthy controls (n = 19) (P < 0.001), and IL-25, TSLP and IL-33 mRNA levels were concomitantly increased (P < 0.001). Additionally, TRPM8 mRNA levels correlated strongly with those of IL-25 and TSLP (P < 0.001), and TRPM8 protein levels were significantly higher in bronchodilator-responsive asthmatic subjects than in nonresponders. @*Conclusions@#TRPM8 may be involved in the airway epithelial cell innate immune response and a molecular target for the treatment of asthma.

12.
Article in English | WPRIM | ID: wpr-896604

ABSTRACT

Grilling, a common cooking method worldwide, can produce more toxic gases than other cooking methods. However, the impact of frequently grilling meat or fish at home on airflow limitation in adult asthma has not been well elucidated. We performed a prospective cohort study of 91 adult patients with asthma enrolled from 2 university hospitals. Of the patients, 39 (42.9%) grilled meat or fish at least once a week and 52 (57.1%) less than once a week. Patients who grilled at least once a week tended to have lower peak expiratory flow rate (PEFR) than those who grilled less than once a week (median, 345.5 L/min; 95% confidence interval [CI], 291.8–423.2 L/min vs. median, 375.1 L/min; 95% CI, 319.7–485.7 L/min; P = 0.059). Among patients with severe asthma who received step 4–5 treatment, PEFR was significantly lower in patients who grilled at least once a week compared with those who grilled less than once a week (median, 297.8 L/min; 95% CI, 211.3–357.7 L/min vs. median, 396.1 L/min; 95% CI, 355.0–489.6 L/min; P < 0.001). Our results suggest that the frequency of grilling meat or fish at home may affect PEFR in asthmatic patients, especially those with severe asthma who needed a high level of asthma treatment.

13.
Article in English | WPRIM | ID: wpr-896444

ABSTRACT

For the past three decades, more than a thousand of genetic studies have been performed to find out the genetic variants responsible for the risk of asthma. Until now, all of the discovered single nucleotide polymorphisms have explained genetic effects less than initially expected. Thus, clarification of environmental factors has been brought up to overcome the ‘missing’ heritability. The most exciting solution is epigenesis because it intervenes at the junction between the genome and the environment. Epigenesis is an alteration of genetic expression without changes of DNA sequence caused by environmental factors such as nutrients, allergens, cigarette smoke, air pollutants, use of drugs and infectious agents during pre- and post-natal periods and even in adulthood. Three major forms of epigenesis are composed of DNA methylation, histone modifications, and specific microRNA. Recently, several studies have been published on epigenesis in asthma and allergy as a powerful tool for research of genetic heritability in asthma albeit epigenetic changes are at the starting point to obtain the data on specific phenotypes of asthma. In this presentation, we mainly review the potential role of DNA CpG methylation in the risk of asthma and its sub-phenotypes including nonsteroidal anti-inflammatory exacerbated respiratory diseases.

14.
Article in English | WPRIM | ID: wpr-888903

ABSTRACT

Purpose@#Cold air is a major environmental factor that exacerbates asthma. Transient receptor potential melastatin family member 8 (TRPM8) is a cold-sensing channel expressed in the airway epithelium. However, its role in airway inflammation remains unknown. We investigated the role of TRPM8 in innate immune responses in bronchial epithelial cells and asthmatic subjects. @*Methods@#The TRPM8 mRNA and protein expression on BEAS2B human bronchial epithelial cells was examined by real-time polymerase chain reaction (PCR), immunofluorescence staining and western blotting. Additionally, interleukin (IL)-4, IL-6, IL-8, IL-13, IL-25 and thymic stromal lymphopoietin (TSLP) levels before and after menthol, dexamethasone and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) treatments were measured via real-time PCR. TRPM8 protein levels in the supernatants of induced sputum from asthmatic subjects and normal control subjects were measured using enzyme-linked immunosorbent assay, and mRNA levels in sputum cell lysates were measured using real-time PCR. @*Results@#Treatment with up to 2 mM menthol dose-dependently increased TRPM8 mRNA and protein in BEAS2B cells compared to untreated cells (P < 0.001) and concomitantly increased IL-25 and TSLP mRNA (P < 0.05), but not IL-33 mRNA. BCTC (10 μM) significantly abolished menthol-induced up-regulation of TRPM8 mRNA and protein and IL-25 and TSLP mRNA (P < 0.01). TRPM8 protein levels were higher in the supernatants of induced sputum from asthmatic subjects (n = 107) than in those from healthy controls (n = 19) (P < 0.001), and IL-25, TSLP and IL-33 mRNA levels were concomitantly increased (P < 0.001). Additionally, TRPM8 mRNA levels correlated strongly with those of IL-25 and TSLP (P < 0.001), and TRPM8 protein levels were significantly higher in bronchodilator-responsive asthmatic subjects than in nonresponders. @*Conclusions@#TRPM8 may be involved in the airway epithelial cell innate immune response and a molecular target for the treatment of asthma.

15.
Article in English | WPRIM | ID: wpr-888900

ABSTRACT

Grilling, a common cooking method worldwide, can produce more toxic gases than other cooking methods. However, the impact of frequently grilling meat or fish at home on airflow limitation in adult asthma has not been well elucidated. We performed a prospective cohort study of 91 adult patients with asthma enrolled from 2 university hospitals. Of the patients, 39 (42.9%) grilled meat or fish at least once a week and 52 (57.1%) less than once a week. Patients who grilled at least once a week tended to have lower peak expiratory flow rate (PEFR) than those who grilled less than once a week (median, 345.5 L/min; 95% confidence interval [CI], 291.8–423.2 L/min vs. median, 375.1 L/min; 95% CI, 319.7–485.7 L/min; P = 0.059). Among patients with severe asthma who received step 4–5 treatment, PEFR was significantly lower in patients who grilled at least once a week compared with those who grilled less than once a week (median, 297.8 L/min; 95% CI, 211.3–357.7 L/min vs. median, 396.1 L/min; 95% CI, 355.0–489.6 L/min; P < 0.001). Our results suggest that the frequency of grilling meat or fish at home may affect PEFR in asthmatic patients, especially those with severe asthma who needed a high level of asthma treatment.

16.
Article in English | WPRIM | ID: wpr-719693

ABSTRACT

For the past three decades, a large number of genetic studies have been performed to examine genetic variants associated with asthma and its subtypes in hopes of gaining better understanding of the mechanisms underlying disease pathology and to identify genetic biomarkers predictive of disease outcomes. Various methods have been used to achieve these objectives, including linkage analysis, candidate gene polymorphism analysis, and genome-wide association studies (GWAS); however, the degree to which genetic variants contribute to asthma pathogenesis has proven to be much less significant than originally expected. Subsequent application of GWAS to well-defined phenotypes, such as occupational asthma and non-steroidal anti-inflammatory drugexacerbated respiratory diseases, has overcome some of these limitations, although with only partial success. Recently, a combinatorial analysis of single nucleotide polymorphisms (SNPs) identified by GWAS has been used to develop sets of genetic markers able to more accurately stratify asthma subtypes. In this review, we discuss the implications of the identified SNPs in diagnosis of asthma and its subtypes and the progress being made in combinatorial analysis of genetic variants.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Aspirin , Asthma , Asthma, Occupational , Biomarkers , Diagnosis , Genetic Association Studies , Genetic Markers , Genetic Techniques , Genome-Wide Association Study , Hope , Pathology , Phenotype , Polymorphism, Single Nucleotide
17.
Article in English | WPRIM | ID: wpr-762171

ABSTRACT

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) has attracted a great deal of attention because of its association with severe asthma. However, it remains widely underdiagnosed in asthmatics as well as the general population. Upon pharmacological inhibition of cyclooxygenase 1 by NSAIDs, production of anti-inflammatory prostaglandin E2 and lipoxins ceases, while release of proinflammatory cysteinyl leukotrienes increases. To determine the underlying mechanisms, many studies have attempted to elucidate the genetic variants, such as single nucleotide polymorphisms, responsible for alterations of prostaglandins and leukotrienes, but the results of these genetic studies could not explain the whole genetic pathogenesis of NERD. Accordingly, the field of epigenetics has been introduced as an additional contributor to genomic alteration underlying the development of NERD. Recently, changes in CpG methylation, as one of the epigenetic components, have been identified in target tissues of NERD. This review discusses in silico analyses of both genetic and epigenetic components to gain a better understanding of their complementary roles in the development of NERD. Although the molecular mechanisms underlying NERD pathogenesis remain poorly understood, genetic and epigenetic variations play significant roles. Our results enhance the understanding of the genetic and epigenetic mechanisms involved in the development of NERD and suggest new approaches toward better diagnosis and management.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Asthma , Computer Simulation , Cyclooxygenase 1 , Diagnosis , Dinoprostone , Epigenomics , Genetics , Leukotrienes , Lipoxins , Methylation , Polymorphism, Single Nucleotide , Prostaglandins
18.
Article in English | WPRIM | ID: wpr-719513

ABSTRACT

PURPOSE: Although mild to moderate asthma is much more common, the morbidity and mortality of severe asthma are much higher. This study was performed to identify and analyze the clinical characteristics of severe asthma in Korea. METHODS: We registered patients with severe refractory asthma into the Severe Asthma Registry supported by the Severe Asthma Work Group of the Korean Academy of Asthma, Allergy and Clinical Immunology. Patients were enrolled since 2010 from the 15 university hospitals nationwide in Korea. Severe asthma was defined according to modified European Respiratory Society/American Thoracic Society criteria. Information on demographics, medical history, pulmonary function tests and skin prick tests was collected; the clinical characteristics of severe asthmatics were analyzed from the collected data. RESULTS: A total of 489 patients were enrolled with a mean age of 62.3; 45% are male. Sixty percent of patients received Global Initiative for Asthma step 4 treatment, and 30% received step 5 treatment. The most common comorbidities were allergic rhinitis (58.7%). Aspirin hypersensitivity was observed in 14.0%. Approximately half (53.9%) are non-smokers. Atopy was proven in 38.5% of the patients. Regarding asthma medications, inhaled corticosteroids and long-acting β-agonist combination inhalers were most commonly prescribed (96.5%), followed by leukotriene antagonists (71.0%). A recombinant anti-immunoglobulin E monoclonal antibody (omalizumab) has been used in 1.8% of the patients. The mean forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and FEV1/FVC were 78.7%, 67.5% and 67.9% of predicted values, respectively. The mean Asthma Control Test and quality of life questionnaire scores were 16.5 out of 25 and 59.5 out of 85, respectively. CONCLUSIONS: The baseline characteristics of severe asthma patients in the Korea Severe Asthma Registry were analyzed and reported for the first time. With this cohort, further prospective studies should be performed to search for ways to improve management of severe refractory asthma.


Subject(s)
Adrenal Cortex Hormones , Adult , Allergy and Immunology , Aspirin , Asthma , Cohort Studies , Comorbidity , Demography , Forced Expiratory Volume , Hospitals, University , Humans , Hypersensitivity , Korea , Leukotriene Antagonists , Male , Mortality , Nebulizers and Vaporizers , Prospective Studies , Quality of Life , Respiratory Function Tests , Rhinitis, Allergic , Skin , Vital Capacity
19.
Article in English | WPRIM | ID: wpr-715652

ABSTRACT

BACKGROUND/AIMS: The methacholine bronchial provocation test (MBPT) is used to detect and quantify airway hyper-responsiveness (AHR). Since improvements in the severity of asthma are associated with improvements in AHR, clinical studies of asthma therapies routinely use the change of airway responsiveness as an objective outcome. The aim of this study was to assess the relationship between serial MBPT and clinical profiles in patients with asthma. METHODS: A total of 323 asthma patients were included in this study. The MBPT was performed on all patients beginning at their initial diagnosis until asthma was considered controlled based on the Global Initiative for Asthma guidelines. A responder was defined by a decrease in AHR while all other patients were considered non-responders. RESULTS: A total of 213 patients (66%) were responders, while 110 patients (34%) were non-responders. The responder group had a lower initial PC20 (provocative concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20%) and longer duration compared to the non-responder group. Members of the responder group also had superior qualities of life, compared to members of the non-responder group. Whole blood cell counts were not related to differences in PC20; however, eosinophil concentration was. No differences in sex, age, body mass index, smoking history, serum immunoglobulin E, or frequency of acute exacerbation were observed between responders and non-responders. CONCLUSIONS: The initial PC20, the duration of asthma, eosinophil concentrations, and quality-of-life may be useful variables to identify improvements in AHR in asthma patients.


Subject(s)
Asthma , Blood Cell Count , Body Mass Index , Bronchial Provocation Tests , Diagnosis , Eosinophils , Forced Expiratory Volume , Humans , Immunoglobulin E , Immunoglobulins , Methacholine Chloride , Respiratory Hypersensitivity , Smoke , Smoking
20.
Article in English | WPRIM | ID: wpr-718134

ABSTRACT

PURPOSE: Asthma is a heterogeneous disease that responds to medications to varying degrees. Cluster analyses have identified several phenotypes and variables related to fixed airway obstruction; however, few longitudinal studies of lung function have been performed on adult asthmatics. We investigated clinical, demographic, and inflammatory factors related to persistent airflow limitation based on lung function trajectories over 1 year. METHODS: Serial post-bronchodilator forced expiratory volume (FEV) 1% values were obtained from 1,679 asthmatics who were followed up every 3 months for 1 year. First, a hierarchical cluster analysis was performed using Ward's method to generate a dendrogram for the optimum number of clusters using the complete post-FEV1 sets from 448 subjects. Then, a trajectory cluster analysis of serial post-FEV1 sets was performed using the k-means clustering for the longitudinal data trajectory method. Next, trajectory clustering for the serial post-FEV1 sets of a total of 1,679 asthmatics was performed after imputation of missing post-FEV1 values using regression methods. RESULTS: Trajectories 1 and 2 were associated with normal lung function during the study period, and trajectory 3 was associated with a reversal to normal of the moderately decreased baseline FEV1 within 3 months. Trajectories 4 and 5 were associated with severe asthma with a marked reduction in baseline FEV1. However, the FEV1 associated with trajectory 4 was increased at 3 months, whereas the FEV1 associated with trajectory 5 was persistently disturbed over 1 year. Compared with trajectory 4, trajectory 5 was associated with older asthmatics with less atopy, a lower immunoglobulin E (IgE) level, sputum neutrophilia and higher dosages of oral steroids. In contrast, trajectory 4 was associated with higher sputum and blood eosinophil counts and more frequent exacerbations. CONCLUSIONS: Trajectory clustering analysis of FEV1 identified 5 distinct types, representing well-preserved to severely decreased FEV1. Persistent airflow obstruction may be related to non-atopy, a low IgE level, and older age accompanied by neutrophilic inflammation and low baseline FEV1 levels.


Subject(s)
Adult , Airway Obstruction , Asthma , Disease Progression , Eosinophils , Forced Expiratory Volume , Humans , Immunoglobulin E , Immunoglobulins , Inflammation , Longitudinal Studies , Lung , Methods , Neutrophils , Phenotype , Sputum , Steroids
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