ABSTRACT
Background@#Some reports have suggested that the clinical and economic burdens of asthma are associated with blood eosinophil levels. The association between clinical burden and blood eosinophil counts were evaluated in a Korean adult asthma cohort. @*Methods@#Clinical information including blood eosinophil counts that were not affected by systemic corticosteroids were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea database. Clinical burden was defined as 1) asthma control status, 2) medication demand and 3) acute exacerbation (AE) events during 1 consecutive year after enrollment. All patients were divided into atopic and non-atopic asthmatics. The associations between asthma outcomes and the blood eosinophil count were evaluated. @*Results@#In total, 302 patients (124 atopic and 178 non-atopic asthmatics) were enrolled. In all asthmatics, the risk of severe AE was higher in patients with blood eosinophil levels < 100 cells/µL than in patients with levels ≥ 100 cells/µL (odds ratio [OR], 5.406; 95% confidence interval [CI], 1.266–23.078; adjusted P = 0.023). Among atopic asthmatics, the risk of moderate AE was higher in patients with blood eosinophil levels ≥ 300 cells/µL than in patients with levels < 300 cells/µL (OR, 3.558; 95% CI, 1.083–11.686; adjusted P = 0.036). Among non-atopic asthmatics, the risk of medication of Global Initiative for Asthma (GINA) steps 4 or 5 was higher in patients with high blood eosinophil levels than in patients with low blood eosinophil levels at cutoffs of 100, 200, 300, 400, and 500 cells/µL. @*Conclusion@#The baseline blood eosinophil count may predict the future clinical burden of asthma.
ABSTRACT
Asthma is a heterogeneous disease whose development is shaped by a variety of environmental and genetic factors. While several recent studies suggest that microbial dysbiosis in the gut may promote asthma, little is known about the relationship between the recently discovered lung microbiome and asthma. Innate lymphoid cells (ILCs) have also been shown recently to participate in asthma. To investigate the relationship between the lung microbiome, ILCs, and asthma, we recruited 23 healthy controls (HC), 42 patients with non-severe asthma, and 32 patients with severe asthma. Flow cytometry analysis showed severe asthma associated with fewer natural cytotoxicity receptor (NCR) + ILC3s in the lung.Similar changes in other ILC subsets, macrophages, and monocytes were not observed. The asthma patients did not differ from the HC in terms of the alpha and beta-diversity of the lung and gut microbiomes. However, lung function correlated positively with both NCR + ILC3 frequencies and microbial diversity in the lung. Sputum NCR + ILC3 frequencies correlated positively with lung microbiome diversity in the HC, but this relationship was inversed in severe asthma. Together, these data suggest that airway NCR + ILC3s may contribute to a healthy commensal diversity and normal lung function.
ABSTRACT
Purpose@#Adverse transfusion reactions (ATRs) are unfavorable reactions to the transfused unit, and the severity may be different among individuals, depending upon the type of reactions and the patient’s susceptibility. It is necessary to operate and manage a systematic monitoring system to minimize these ATRs and increase the safety. This study was conducted to evaluate clinical features of transfusion-related adverse events and morbidities. @*Methods@#We retrospectively analyzed transfusion data from electronic medical records during the recent 3 years (April 2017 to April 2020) at Seoul National University Bundang Hospital. The electronic search strategy was applied to search for the type of blood products prescribed and identify symptoms that occurred during transfusion as recorded in the nursing chart which is based on the International Classification for Nursing Practice. @*Results@#A total of 18,772 people were transfused during the study period. A total of 524 people were reported as suspected ATRs, of whom 466 were finally confirmed. Red blood cell was the most frequent culprit blood product (59.9%), followed by apheresis platelet (25.1%), fresh frozen plasma (10.1%), and platelet (4.9%). Clinical symptoms included fever (54.9%), urticaria and itching (34.7%), chillness and shivering (21.9%), and chest discomfort (6.0%), dyspnea (5.3%), cold sweating (3.8%), hypotension (2.1%), and palpitations (1.9%). The severity of ATRs were mild (91.8%), moderate (7.1%), and severe (1.1%). @*Conclusion@#ATRs are mostly mild, but life-threatening reactions may occur. Physicians should be aware of various features of ATRs to appropriately recognize and treat such patients.
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Purpose@#Asthma is a common chronic lung disease, in which interleukin (IL)-13 is implicated as a central regulator of IgE synthesis, mucus hypersecretion, airway hyperresponsiveness (AHR), and fibrosis. This study was designed to determine the anti-inflammatory effect of atorvastatin, a widely used lipid-lowering agent, on the IL-13-induced lung pathology through the modulation of macrophages. @*Methods@#Atorvastatin (40 mg/kg) was given to transgenic mice overexpressing IL-13 (IL-13 TG mice) and their wild type littermates by oral gavage for 2 weeks. AHR, numbers of inflammatory cells in the airway, and cytokine levels in IL-13 TG mice were measured.Using the alveolar macrophage cell line CRL-2456, the direct effect of atorvastatin on macrophages activated by recombinant IL-13 was assessed. @*Results@#Significant reduction in total leukocytes and alleviation of AHR were observed with administration of atorvastatin in IL-13 TG mice compared to those without atorvastatin treatment (P< 0.05). Atorvastatin administration resulted in upregulation of IL-10 in the lungs of IL-13 TG mice (P< 0.05). In addition, mRNA expression of connective tissue growth factor, fibronectin, and type III collagen as well as chord length enhanced by IL-13 overexpression were reduced by atorvastatin administration (P< 0.05). M2 macrophage markers, such as Ym-1 and CD206, were decreased, while M1 macrophage marker, inducible nitric oxide synthase, was increased upon atorvastatin treatment (P< 0.05). Administration of atorvastatin resulted in improved removal of apoptotic cells (P< 0.05). @*Conclusion@#The results of this study reveal a potential of atorvastatin as an effective antiasthmatic agent by reducing IL-13-induced lung inflammation via the modulation of macrophage polarization.
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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.
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Background/Aims@#Despite proper use of pharmaceuticals, adverse drug reactions (ADRs) can lead to problems related to patient safety. We analyzed the characteristics of ADRs, particularly serious adverse events (SAEs), in a single tertiary medical institution. @*Methods@#Spontaneous ADR report data collected from 2010 to 2019 in Seoul National University Hospital were assessed. Causality was evaluated according to the World Health Organization-Uppsala Monitoring Centre criteria. Age, sex, onset, severity, seriousness, and system organ class (SOC) of ADRs and SAEs were analyzed. @*Results@#During the study period, a total of 49,955 individual case safety reports were assessed as possible, probable, or certain. Although the number of gastrointestinal ADR reports was high (25.9%), severe cases were uncommon (2.6%). By contrast, the number of hematologic disorders was low (6.6%) but 39.2% of them were severe. Among ADRs, 10.2% were assessed as SAEs, the proportion of which was high at extreme ages and in males. Body as a whole-general disorders were the most frequently reported SOC for SAEs, followed by skin and appendage disorders. Antineoplastic agents and antibiotics were the most common causative agents of SAEs and ADRs. Anaphylactic reaction was the most frequent SAE (6.5%). @*Conclusions@#The proportion of SAE differs according to SOC and drug. Attention should be paid to SAEs in children and older adults because the rate of SAEs is significantly higher at extreme ages.
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.
ABSTRACT
Background/Aims@#Despite proper use of pharmaceuticals, adverse drug reactions (ADRs) can lead to problems related to patient safety. We analyzed the characteristics of ADRs, particularly serious adverse events (SAEs), in a single tertiary medical institution. @*Methods@#Spontaneous ADR report data collected from 2010 to 2019 in Seoul National University Hospital were assessed. Causality was evaluated according to the World Health Organization-Uppsala Monitoring Centre criteria. Age, sex, onset, severity, seriousness, and system organ class (SOC) of ADRs and SAEs were analyzed. @*Results@#During the study period, a total of 49,955 individual case safety reports were assessed as possible, probable, or certain. Although the number of gastrointestinal ADR reports was high (25.9%), severe cases were uncommon (2.6%). By contrast, the number of hematologic disorders was low (6.6%) but 39.2% of them were severe. Among ADRs, 10.2% were assessed as SAEs, the proportion of which was high at extreme ages and in males. Body as a whole-general disorders were the most frequently reported SOC for SAEs, followed by skin and appendage disorders. Antineoplastic agents and antibiotics were the most common causative agents of SAEs and ADRs. Anaphylactic reaction was the most frequent SAE (6.5%). @*Conclusions@#The proportion of SAE differs according to SOC and drug. Attention should be paid to SAEs in children and older adults because the rate of SAEs is significantly higher at extreme ages.
ABSTRACT
Background/Aims@#Skin (STs) and drug provocation (DPTs) tests are essential for identifying the culprit drugs causing drug hypersensitivity reactions (DHRs). Several protocols have been developed for the identification of some culprit drugs, but they are neither thoroughly validated nor standardized. Furthermore, language barriers may impede the exchange of information necessary for test standardization. @*Methods@#We searched the Korean literature for articles on drug hypersensitivity published from 1933 to 2016 using the KoreaMed search engine and archives of Korean journals. We reviewed and rated all articles according to the description of STs and DPTs. @*Results@#Of the 632 articles obtained in our initial search, 34 had adequate descriptions of 15 STs and 22 DPTs. Up to 27 healthy control subjects in STs were enrolled to determine non-irritating concentrations. The concentrations used for intradermal tests were commonly a 1/10 dilution of those used for skin prick tests. The interpretations of the STs were mostly similar among researchers. For DPTs, most procedures were single-arm open-label tests of various drugs. The initial dose ranged from a quarter dose to a single therapeutic dose, depending on the severity of the original hypersensitivity reaction. The interval between doses was usually 30 to 60 minutes, and a positive reaction usually occurred within twice the time of the original reaction. @*Conclusions@#Efforts to distribute information are necessary to standardize protocols and better understand DHRs.
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Purpose@#Asthma is a chronic airway inflammatory disorder and is associated with macrophages. Statin, a well-known lipid-lowering agent, has recently been noted for its anti-inflammatory effect on macrophage. This study was designed to evaluate the antiasthmatic effect of atorvastatin via modulation of macrophage activation by using an animal model of allergic asthma. @*Methods@#Atorvastatin 40 mg/kg was given by gavage once a day for 3 days before challenge of ovalbumin (OVA); airway hyperresponsiveness (AHR), airway inflammatory cells, and cytokines were evaluated in the murine asthma model. The direct effect of atorvastatin on the activation of macrophages In vitro was determined using the alveolar macrophage cell line CRL-2456. @*Results@#Administration of atorvastatin reduced the numbers of total inflammatory cells, macrophages, and eosinophils as well as lung histology enhanced in the murine asthma model. AHR measured by enhanced pause was significantly reduced after atorvastatin administration in the murine asthma model (P< 0.05). Atorvastatin administration resulted in the reduction in serum OVA-specific IgE levels and the increase in serum OVA-specific IgG2a levels (P< 0.05). The mRNA levels of Ccr3, Il-17, and Muc5ac enhanced by OVA challenge were decreased by treatment with atorvastatin (P< 0.05). Along with these improvement in allergic inflammatory changes, the population of CD11c-CD206+ macrophages as well as the expression of Ym-1 and Relm-α in the lungs were reduced with atorvastatin (P< 0.05). In vitro test with CRL-2456 showed that atorvastatin reduced the expression of Cd206, Arg-1, and Fgf-2 induced by IL-4 stimulation (P< 0.05). @*Conclusion@#This study highlighted the antiasthmatic effect of atorvastatin on the suppression of M2 macrophage activation in allergic asthma.
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Background/Aims@#Tuberculosis has incidence and mortality rates that are among the highest for all communicable diseases. Adverse drug reactions (ADRs) to anti-tubercular drugs are common, and have a major impact on treatment maintenance and prognosis. It is important to understand the characteristics of ADRs and establish a suitable management plan. @*Methods@#We retrospectively reviewed patients with ADRs during treatment with first-line antitubercular drugs such as isoniazid, rifampicin, ethambutol, and pyrazinamide from 2009 to 2018. Age, sex, and total treatment period, and the onset, severity, seriousness, and system organ class of ADRs, were analyzed to understand the characteristics of first-line anti-tubercular drug-related ADRs. @*Results@#A total of 1,606 of 5,482 patients (29.3%) experienced ADRs after administration of first-line anti-tubercular drugs. The incidence of ADRs related to isoniazid, rifampicin, ethambutol, and pyrazinamide was 22.2%, 21.3%, 24.5%, and 29.6%, respectively. A total of 2,098 ADR reports were made (mean of 1.3 ± 0.6 per patient). The rates of mild, moderate, and severe ADRs were 32.4%, 61.1%, and 6.5%, respectively. There were 127 reports (6.1%) of serious ADRs. Skin and appendage disorders were most frequently reported (27.5%), followed by gastrointestinal disorders (17.5%), and liver and biliary system disorders (13.1%). The total treatment period was longer in patients who experienced ADRs (224.0 ± 3.1 days vs. 247.0 ± 4.7 days, p = 0.009). @*Conclusions@#The incidence of ADRs to first-line anti-tuberculosis drugs was 29.3%, and 6.5% were severe ADRS. ADRs prolonged the overall treatment duration, indicating the importance of their detection and management.
ABSTRACT
Purpose@#Rituximab is prone to infusion-related reactions, which commonly requires desensitization to maintain its administration. Conventional desensitization protocols are using multistep infusion by diluting solutions. However, the process of diluting drugs and stepwise delivery needs additional time and effort. The objective of this study was to investigate the safety and efficacy of a nondiluting, one-bag protocol of rituximab desensitization. @*Methods@#A retrospective study was performed by reviewing the medical records of patients who underwent rituximab desensitization between 2009 and 2018. The completion rate, occurrence and severity of breakthrough reactions (BTR), and time required to complete the therapy were compared between one-bag protocol and multibag protocol. Results were analyzed by generalized estimation equation method, and odds ratios (ORs) of completion rate and BTR incidence were estimated. @*Results@#Total 190 cases of desensitization therapy were performed in 49 patients; the incidence of BTR was 16.84% and the overall completion rate was 96.32%. No significant difference in completion rate was found (OR, 3.58; 95% confidence interval [CI], 0.79– 16.38) and there was no significant difference in BTR incidence (OR, 0.81; 95% CI, 0.23–2.82) in one-bag protocol. BTR in the one-bag protocol tended to occur even through entire steps, whereas most of the BTR in the multibag protocol occurred at later steps of the process. The average time spent in the desensitization was 60 minutes shorter in the one-bag than the multibag protocol (258.15 minutes vs. 329.81 minutes, P< 0.001). @*Conclusion@#One-bag desensitization protocol showed no significant difference in safety and efficiency compared to the conventional multibag protocol, with shortening the time required for completion.
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Background@#Voriconazole, a triazole antifungal agent exhibits broad-spectrum antifungal activity. It is used to treat severe, invasive fungal infections, including invasive aspergillosis and candidemia. The aim of this study was to assess the pharmacokinetic equivalence of a test formulation (Vorico® Injection) and reference formulation (Vfend® IV) of voriconazole. @*Materials and Methods@#This was a randomized, open-label, single-dose, three-group, two-treatment, two-sequence, two-period, crossover phase I trial with 7-day washout periods (ClinicalTrials.gov identifier NCT02631954). Twenty-four healthy Korean male subjects were recruited. In each group, eight subjects were randomized in a 1:1 manner to receive a single dose of 200 mg test or reference formulation intravenously over 1.5 h. Blood samples were collected over 24 h post-dose, and plasma drug concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined using a non-compartmental analysis, and safety was evaluated. @*Results@#Twenty-three subjects completed the study. The geometric mean ratio (90% confidence interval) of the test formulation to reference formulation was 0.9570 (0.8178 – 1.1199) for the maximum plasma concentration (Cmax) and 1.0720 (1.0262 – 1.1198) for the area under the concentration–time curve from dosing to the last quantifiable concentration (AUClast). The mean plasma concentration–time profiles, pharmacokinetic parameters, and safety were comparable between the two formulations. @*Conclusion@#Equivalent pharmacokinetic characteristics that satisfied the criteria of bioequivalence and similar safety profiles were observed for both test and reference formulations of voriconazole.
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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 , Humans , Male , Airway Obstruction , Asthma , Bayes Theorem , Cohort Studies , Delivery of Health Care , Eosinophils , Follow-Up Studies , Forced Expiratory Volume , Logistic Models , Risk Factors , Vital CapacityABSTRACT
BACKGROUND: There could be a gap between asthma management guidelines and current practice. We evaluated the awareness of and compliance with asthma management guidelines, and the internal and external barriers to compliance, for the first time in Korea.METHODS: From March to September of 2012, 364 physicians treating asthma patients at primary, secondary, and tertiary teaching hospitals were enrolled. They completed a questionnaire on the awareness of and compliance with asthma management guidelines, and the barriers and alternatives to their implementation.RESULTS: Of the 364 physicians, 79.1% were men and 56.9% were primary care physicians. The mean age was 40.5 ± 11.2 years. Most of them were aware of asthma management guidelines (89.3%). However, only a portion (11.0%) of them complied with the guidelines for asthma. Pulmonary function tests for diagnosis of asthma were performed by 20.1% of all physicians and 9.2% of primary care physicians, and by 9.9% of all physicians and 5.8% of primary care physicians for monitoring. Physicians stated that ‘asthma monitoring’ was the most difficult part of the guidelines, followed by ‘environmental control and risk factors.’ Only 39.6% (31.9% of the primary care physicians) prescribed an inhaled corticosteroid (ICS) as the first-line treatment for persistent asthma. The internal barriers were physician's preference for oral medications, difficulty in use even with inhaler training, and concern over ICS side effects. The external barriers were possible rejection of medical reimbursement by health insurance, refusal by the patient, cost, and a poor environment for teaching the patient how to use the inhaler. Alternatives proposed by physicians to implement asthma management guidelines were to improve medical reimbursement policies and the level of awareness of such guidelines.CONCLUSION: Compliance with the asthma management guidelines, including ICS prescription, is low despite the awareness of the guidelines. It is necessary to develop a strategy to overcome the internal and external barriers.
ABSTRACT
BACKGROUND@#There could be a gap between asthma management guidelines and current practice. We evaluated the awareness of and compliance with asthma management guidelines, and the internal and external barriers to compliance, for the first time in Korea.@*METHODS@#From March to September of 2012, 364 physicians treating asthma patients at primary, secondary, and tertiary teaching hospitals were enrolled. They completed a questionnaire on the awareness of and compliance with asthma management guidelines, and the barriers and alternatives to their implementation.@*RESULTS@#Of the 364 physicians, 79.1% were men and 56.9% were primary care physicians. The mean age was 40.5 ± 11.2 years. Most of them were aware of asthma management guidelines (89.3%). However, only a portion (11.0%) of them complied with the guidelines for asthma. Pulmonary function tests for diagnosis of asthma were performed by 20.1% of all physicians and 9.2% of primary care physicians, and by 9.9% of all physicians and 5.8% of primary care physicians for monitoring. Physicians stated that ‘asthma monitoring’ was the most difficult part of the guidelines, followed by ‘environmental control and risk factors.’ Only 39.6% (31.9% of the primary care physicians) prescribed an inhaled corticosteroid (ICS) as the first-line treatment for persistent asthma. The internal barriers were physician's preference for oral medications, difficulty in use even with inhaler training, and concern over ICS side effects. The external barriers were possible rejection of medical reimbursement by health insurance, refusal by the patient, cost, and a poor environment for teaching the patient how to use the inhaler. Alternatives proposed by physicians to implement asthma management guidelines were to improve medical reimbursement policies and the level of awareness of such guidelines.@*CONCLUSION@#Compliance with the asthma management guidelines, including ICS prescription, is low despite the awareness of the guidelines. It is necessary to develop a strategy to overcome the internal and external barriers.
ABSTRACT
BACKGROUND@#There could be a gap between asthma management guidelines and current practice. We evaluated the awareness of and compliance with asthma management guidelines, and the internal and external barriers to compliance, for the first time in Korea.@*METHODS@#From March to September of 2012, 364 physicians treating asthma patients at primary, secondary, and tertiary teaching hospitals were enrolled. They completed a questionnaire on the awareness of and compliance with asthma management guidelines, and the barriers and alternatives to their implementation.@*RESULTS@#Of the 364 physicians, 79.1% were men and 56.9% were primary care physicians. The mean age was 40.5 ± 11.2 years. Most of them were aware of asthma management guidelines (89.3%). However, only a portion (11.0%) of them complied with the guidelines for asthma. Pulmonary function tests for diagnosis of asthma were performed by 20.1% of all physicians and 9.2% of primary care physicians, and by 9.9% of all physicians and 5.8% of primary care physicians for monitoring. Physicians stated that ‘asthma monitoring’ was the most difficult part of the guidelines, followed by ‘environmental control and risk factors.’ Only 39.6% (31.9% of the primary care physicians) prescribed an inhaled corticosteroid (ICS) as the first-line treatment for persistent asthma. The internal barriers were physician's preference for oral medications, difficulty in use even with inhaler training, and concern over ICS side effects. The external barriers were possible rejection of medical reimbursement by health insurance, refusal by the patient, cost, and a poor environment for teaching the patient how to use the inhaler. Alternatives proposed by physicians to implement asthma management guidelines were to improve medical reimbursement policies and the level of awareness of such guidelines.@*CONCLUSION@#Compliance with the asthma management guidelines, including ICS prescription, is low despite the awareness of the guidelines. It is necessary to develop a strategy to overcome the internal and external barriers.
ABSTRACT
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction involving various internal organs. Flare-ups after recovery from the initial presentation of DRESS are caused by relapse of drug-induced T-cell-mediated reactions. However, the specific underlying mechanism is unclear. Here, we report a case of a 60-year-old man with allopurinol-induced DRESS who suffered recurrent episodes of generalized rash with eosinophilia, which mimicked immune reconstitution inflammatory syndrome. Analysis of immunological profiles revealed that the percentages of T lymphocytes and regulatory T cells in the patient with DRESS were higher than those in healthy controls. In addition, there was a notable change in the subtype of monocytes in the patient with DRESS; the percentage of nonclassical monocytes increased, whereas that of classical monocytes decreased. Upon viral infection, nonclassical monocytes exhibited strong pro-inflammatory properties that skewed the immune response toward a Th2 profile, which was associated with persistent flare-ups of DRESS. Taken together, the results increase our understanding of the pathogenesis of DRESS as they suggest that expansion of nonclassical monocytes and Th2 cells drives disease pathogenesis.
Subject(s)
Humans , Middle Aged , Allopurinol , Drug Hypersensitivity Syndrome , Eosinophilia , Exanthema , Herpesviridae , Immune Reconstitution Inflammatory Syndrome , Monocytes , Recurrence , T-Lymphocytes , T-Lymphocytes, Regulatory , Th2 CellsABSTRACT
PURPOSE: To identify causative agents of the drug-induced anaphylaxis (DIA) by using the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System (KIDS-KAERS) database (Ministry of Food and Drug Safety) in Korea and to check their labeling information regarding anaphylaxis.METHODS: Among Individual Case Safety Reports from January, 2008 to December 2017, cases of DIA were analyzed for demographics, causative agents and fatal cases resulting in death. The domestic drug labeling, Micromedex and U.S. Food and Drug Administration (FDA) drug package insert, were reviewed to check if the labeling information on suspected causative agents contains anaphylaxis.RESULTS: A total of 4,700 cases of DIA were analyzed. The mean age was 49.85±18.32 years, and 2,642 patients (56.2%) were females. Among 8,664 drugs reported as causative agents, antibiotics (27.4%) accounted for the largest portion. There were 18 fatal cases: antibiotics (7 cases), antineoplastic agents (4 cases) were the major causative drugs for the mortality cases. Of 513 drugs reported as suspected causative agents, 103 (20.1%) did not list anaphylaxis as an adverse effect on domestic drug labeling and 16 (3.1%) did not reflect anaphylaxis in any of 3 adverse drug information.CONCLUSION: Analysis of 10-year data showed that antibiotics were the main cause of DIA and the mortality rate was 0.7%. In 3.1% of suspected drugs, there was no description of anaphylaxis in any of the drug labeling.
Subject(s)
Female , Humans , Anaphylaxis , Anti-Bacterial Agents , Antineoplastic Agents , Demography , Drug Labeling , Korea , Mortality , Pharmacovigilance , United States Food and Drug AdministrationABSTRACT
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.