Report on the methacholine bronchial provocation test protocol: An updated statement of Korean Academy of Asthma, Allergy and Clinical Immunology

The Korean Academy of Asthma, Allergy, and Clinical Immunology task force report aims to provide new protocols for methacholine challenge test (MCT). Although new devices have different delivery system compared to old ones, previous protocols are still used, which cannot guarantee adequate diagnoses of asthma. Another important issue is the recent recommendation in European Respiratory Society (ERS) technical standard guideline to use a delivered methacholine dose that causes a 20% decrease in forced expiratory volume in 1 second (FEV1) (PD 20). Although the previous protocol based on the methacholine concentration causing a 20% decrease in FEV1 (PC 20) has been used globally, several studies have reported that PD 20 is more reliable and applicable for new protocols of MCT. Indeed, a tidal breathing inhalation protocol using a breath-actuated or continuous nebulizer is recommended. Herein, we recommend 3 protocols for the MCT using new devices and provide a brief summary of the change in strategy based on the updated ERS guideline.

A Multicenter Study to Identify the Respiratory Pathogens Associated with Exacerbation of Chronic Obstructive Pulmonary Disease in Korea / 결핵및호흡기질환

Background@#Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea. @*Methods@#A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed. @*Results@#We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016). @*Conclusion@#Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

Retinol-binding protein-4 was associated with sensitization to inhalant allergens in the elderly population

Background/Aims@#Recent evidence suggests an association between allergic sensitization and metabolic markers. However, this association has rarely been examined in the elderly. Retinol-binding protein-4 (RBP-4) is a recently identified adipokine that acts on the muscle and liver affecting insulin sensitivity. We evaluated the association between metabolic parameters and allergic sensitization in the elderly. @*Methods@#We analysed the database of the Korean Longitudinal Study on Health and Aging cohort study conducted during 2005 to 2006. Atopy was identified by inhalant allergen skin prick test. Metabolic conditions were assessed using anthropometric indices and serum biomarkers such as fasting glucose, lipid, adiponectin, and RBP-4. @*Results@#Among the 854 elderly subjects, 17.2% had atopy. Plasma RBP-4 levels were significantly higher in the atopic elderly than nonatopic elderly (p = 0.003). When RBP-4 percentiles were categorized as under three groups, the prevalence of atopy and current rhinitis increased significantly with percentiles of RBP-4 levels (p = 0.019 and p = 0.007, respectively). Log RBP-4 was associated with atopy (odds ratio [OR], 4.10; p = 0.009) and current rhinitis (OR, 2.73; p = 0.014), but not with current asthma (OR, 1.17; p = 0.824). Higher RBP-4 level in atopic elderly was also observed in current rhinitis patients. Atopy, but not current rhinitis, showed significant relationships with log RBP-4 levels in multivariate analyses adjusted for other metabolic markers including body mass index. @*Conclusions@#RBP-4 positively associated with atopy in the general elderly population irrespective of other metabolic markers.

Incidence of teicoplanin adverse drug reactions among patients with vancomycin-associated adverse drug reactions and its risk factors

Background/Aims@#Teicoplanin can be used as an alternative to vancomycin when treating beta-lactam-resistant gram-positive bacterial infections. Both vancomycin and teicoplanin are associated with relatively high rates of adverse drug reactions (ADRs), including hypersensitivity reactions. There is limited data on teicoplanin-vancomycin cross-reactivity. This study examined the incidence of teicoplanin ADRs and risk factors for cross-reactivity between vancomycin and teicoplanin. @*Methods@#We analyzed the incidence of teicoplanin ADRs in a retrospective study of 304 newly teicoplanin-exposed, immunocompetent, hospitalized patients at a single Korean Medical Center between January 1, 2006 and December 31, 2015. @*Results@#Among 304 patients, 238 (78.3%) experienced vancomycin-associated ADRs prior to their teicoplanin exposure and 58 (19.1%) experienced teicoplanin- associated ADRs, which were mostly hypersensitivity reactions without acute kidney injury. The incidence of teicoplanin ADRs was higher in patients who previously experienced vancomycin-related ADRs (23.1% vs. 5.3%, p < 0.001). History of drug allergy was a statistically significant risk factor of teicoplanin ADRs. The incidence of teicoplanin ADRs significantly increased in patients with multiple organ involvement in vancomycin hypersensitivity reactions. @*Conclusions@#Teicoplanin should be administered with caution and clinicians must consider the risk factors of cross-reaction when prescribing teicoplanin to individuals with a history of vancomycin hypersensitivity.

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Drug hypersensitivity reactions in Asia: regional issues and challenges

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Different Biological Pathways Are Up-regulated in the Elderly With Asthma: Sputum Transcriptomic Analysis

BACKGROUND: Elderly asthma (EA) is increasing, but the pathogenesis is unclear. This study aimed to identify EA-related biological pathways by analyzing genome-wide gene expression profiles in sputum cells. METHODS: A total of 3,156 gene probes with significantly differential expressions between EA and healthy elderly controls were used for a hierarchical clustering of genes to identify gene clusters. Gene set enrichment analysis provided biological information, with replication from Gene Expression Omnibus expression profiles. RESULTS: Fifty-five EA patients and 10 elderly control subjects were enrolled. Two distinct gene clusters were found. Cluster 1 (n = 35) showed a lower eosinophil proportion in sputum and less severe airway obstruction compared to cluster 2 (n = 20). The replication data set also identified 2 gene clusters (clusters 1' and 2'). Among 5 gene sets significantly enriched in cluster 1 and 3 gene sets significantly enriched in cluster 2, we confirmed that 2 were significantly enriched in the replication data set (OXIDATIVE_PHOSPHORYLATION gene set in cluster 1 and EPITHELIAL MESENCHYMAL TRANSITION gene set in cluster 2'). CONCLUSIONS: The findings of 2 distinct gene clusters in EA and different biological pathways in each gene cluster suggest 2 different pathogenesis mechanisms underlying EA.

Concurrent bilateral juvenile temporal arteritis and hypereosinophilic syndrome: a case report and review of the literature

Most of temporal arteritis occurs in the older patient over 50 years old, and the histopathologic finding shows a granulomatous inflammation, so this called giant cell arteritis. However, the young patients also present with a nodular lesion in their temple, and juvenile temporal arteritis (JTA) should be considered as one of the differential diagnosis, although it is very rare. For both diagnosis and treatment of JTA, excisional biopsy is essential. The pathologic finding of the temporal artery shows panarteritis with lymphoeosinophilic infiltrates, but no giant cell or granulomatous lesion. JTA is a localized disease with low level of systemic inflammatory marker, so the symptom is usually relieved by excision of affected lesion. Peripheral blood eosinophilia present in some cases of JTA, but its relation with clinical course and prognosis is not yet been known. Herein, we report the case of a 24-year-old man diagnosed with concurrent JTA and hypereosinophilic syndrome. We also reviewed the literature of JTA focusing on the impact of combined peripheral eosinophilia on the course of the disease. Combined peripheral eosinophilia may increase the risk of recurrence of JTA after local treatment such as excision only.

Changes in basophil activation during immunotherapy with house dust mite and mugwort in patients with allergic rhinitis

BACKGROUND: The basophil activation test (BAT) is a promising tool for monitoring allergen-specific immunotherapy responses. OBJECTIVE: We aimed to investigate the changes in basophil activation in response to the inhalant allergens of house dust mite (HDM) and mugwort pollen during immunotherapy in patients with allergic rhinitis. METHODS: We enrolled patients with allergic rhinitis who were to receive subcutaneous immunotherapy for the inhalant allergens HDM or mugwort. A BAT was performed to assess CD63 upregulation in response to allergen stimulation using peripheral blood collected from the patients prior to immunotherapy and at 3, 6, 12, and 24 months after beginning immunotherapy. Rhinitis symptoms were evaluated using the rhinitis quality of life questionnaire (RQLQ) at 1-year intervals. RESULTS: Seventeen patients (10 with HDM sensitivity, 3 with mugwort sensitivity, and 4 with sensitivity to both HDM and mugwort) were enrolled in the study. Basophil reactivity to HDM did not change significantly during 24 months of immunotherapy. However, a significant reduction in basophil reactivity to mugwort was observed at 24-month follow-up. There was no significant association between the change in clinical symptoms by RQLQ and the change in basophil reactivity to either allergen. The change in allergen-specific basophil reactivity to HDM was well correlated with the change in nonspecific basophil activation induced by anti-FcεRI antibody, although basophil reactivity to anti-FcεRI antibody was not significantly reduced during immunotherapy. CONCLUSION: Suppression of CD63 upregulation in the BAT was only observed with mugwort at 2-year follow-up. However, the basophil response did not reflect the clinical response to immunotherapy.

Bullous hemorrhagic dermatosis due to enoxaparin use in a bullous pemphigoid patient

Adverse reactions of subcutaneous low molecular weight heparin or unfractionated heparin could be complications by bleeding, heparin-induced thrombocytopenia, drug-induced liver injury, osteoporosis, and cutaneous reactions. Heparin-induced skin lesions vary from allergic reactions like erythema, urticaria, eczema to intradermal microvascular thrombosis associated with heparin-induced thrombocytopenia. There is a rare cutaneous complication, called bullous hemorrhagic dermatosis. We experienced this rare case of the cutaneous complication caused by enoxaparin. Several tense bullous hemorrhagic lesions occurred after 3 days of enoxaparin in a known bullous pemphigoid patient who had aortic valve replacement surgery with a mechanical prosthesis. The bullous hemorrhagic lesions were regressed after the discontinuation of enoxaparin but recurred after re-administration. The lesions were controlled by the administration of systemic corticosteroid and alternative anticoagulant. To date, less than 20 cases have been reported worldwide. This is the first case of bullous hemorrhagic dermatosis induced by enoxaparin, a low-molecular-weight heparin in Korea. This is also the first case of bullous hemorrhagic dermatosis in a known bullous pemphigoid patient.

Fixed Food Eruption Caused by Actinidia arguta (Hardy Kiwi): A Case Report and Literature Review

Fixed drug eruption (FDE) is a common hypersensitivity reaction characterized by recurrent, well-circumscribed, erythematous patches that arise at the same site as a result of systemic drug exposure. However, fixed food eruption (FFE), a lesion triggered by food ingestion, is a rare allergy that was first defined in 1996. Based on their anti-inflammatory and anti-oxidant properties, the fruit and leaves of Actinidia arguta, the hardy kiwi, are widely consumed across Korea, Japan, and China. This report describes the first case of FFE caused by hardy kiwi leaves, known as Daraesun in Korean, confirmed by oral provocation tests and skin biopsy.

Analysis of Adverse Drug Reactions in Elderly Patients Based on a Spontaneous Reporting System in a Single Tertiary Hospital / 대한내과학회지

BACKGROUND/AIMS: Several factors contribute to the greater propensity for adverse drug reactions (ADRs) in the elderly, including the use of multiple drugs and pharmacokinetic and pharmacodynamic alterations due to aging. We evaluated the characteristics of ADRs in elderly versus younger adults. METHODS: ADRs were collected from a spontaneous reporting system at Seoul National University Hospital from February 2010 to September 2013. We analyzed causative drugs, clinical manifestations, and the severity of ADRs. RESULTS: In total, 15,541 ADRs were reported in patients 18 years of age or older. Common causative drug categories included nervous system, anti-neoplastics, and anti-infectives. The prevalence of ADRs due to respiratory drugs and cardiovascular drugs was higher in the elderly group (≥ 60 years) than in other groups. The most common clinical types were gastrointestinal and skin and appendage issues. The elderly group had a tendency to show a higher proportion of psychiatric, cardiovascular, hematological, and genitourinary symptoms. The proportions of severe ADRs were higher in the elderly groups and in male patients. CONCLUSIONS: Elderly patients were susceptible to ADRs related to respiratory and cardiovascular drugs. Psychiatric, cardiovascular, hematological, and genitourinary disorders account for a higher proportion of ADR symptoms in the elderly than in other age groups. Further efforts to understand, manage, and prevent ADRs in the elderly are required.

Current status of microbiome research in asthma and chronic obstructive pulmonary disease

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by chronic airway inflammation resulting in airflow limitation. They include various phenotypes and endotypes in their disease entities. For that reason, they lack proper biomarkers and epoch-making progresses in treatment nowadays. Healthy airway has been believed to be sterile traditionally. However, with the help of nonculture sequencing techniques, researchers discovered that it is full of the commensal and symbiotic microbial flora. Therefore, microbiome has emerged as a possible biomarker and a clue to understand the pathogenesis of airway disease. Microbiome research in asthma has focused on the association between characteristics of microbiome, such as composition and diversity. However, now it refers to the role of microbiome, including Proteobacteria, in the development and pathogenesis of asthma and allergic diseases. Microbiome research in COPD has revealed its different composition according to the existence and severity of the disease. Also, differences in microbiome composition according to exacerbation state or specific treatment of COPD are reported. Therefore, many researchers pay attention to the possible role of microbiome as a biomarker or a treatment target in asthma and COPD. Herein, we review recent studies on microbiome research in asthma and COPD.

Eosinophilic myocarditis: case series and literature review

Eosinophilic myocarditis is a condition resulting from various eosinophilic diseases, including helminth infection, drug hypersensitivity, systemic vasculitis or idiopathic hypereosinophilic syndromes. Clinical manifestations of eosinophilic myocarditis may vary from early necrosis to endomyocardial fibrosis. Eosinophilic myocarditis is one of the most fatal complications of hypereosinophilia. However, eosinophilic myocarditis has been rarely reported in the literature, particularly in Asia Pacific regions, reflecting the under-recognition of the disease among clinicians. Early recognition is crucial for improving clinical outcomes of eosinophilic myocarditis. Early administration of systemic corticosteroid is necessary in eosinophilic myocarditis regardless of underlying causes, as delayed treatment may result in fatal outcomes. In addition, differential diagnoses of underlying causes for eosinophilia are necessary to improve long-term outcomes.

Physicians' Preferences for Asthma Guidelines Implementation

PURPOSE: Patient care based on asthma guidelines is cost-effective and leads to improved treatment outcomes. However, ineffective implementation strategies interfere with the use of these recommendations in clinical practice. This study investigated physicians' preferences for asthma guidelines, including content, supporting evidence, learning strategies, format, and placement in the clinical workplace. METHODS: We obtained information through a questionnaire survey. The questionnaire was distributed to physicians attending continuing medical education courses and sent to other physicians by airmail, e-mail, and facsimile. RESULTS: A total of 183 physicians responded (male to female ratio, 2.3:1; mean age, 40.4+/-9.9 years); 89.9% of respondents were internists or pediatricians, and 51.7% were primary care physicians. Physicians preferred information that described asthma medications, classified the disease according to severity and level of control, and provided methods of evaluation/treatment/monitoring and management of acute exacerbation. The most effective strategies for encouraging the use of the guidelines were through continuing medical education and discussions with colleagues. Physicians required supporting evidence in the form of randomized controlled trials and expert consensus. They preferred that the guidelines be presented as algorithms or flow charts/flow diagrams on plastic sheets, pocket cards, or in electronic medical records. CONCLUSIONS: This study identified the items of the asthma guidelines preferred by physicians in Korea. Asthma guidelines with physicians' preferences would encourage their implementation in clinical practice.

Colonic Intussusception as a Complication after Colonoscopic Polypectomy / 대한소화기내시경학회지

Intussusception in adults is not common unlike in pediatrics. It also differs from the pediatric intussusception in its origins, symptoms, and treatment. Since more than half of intussusception cases come from malignancy, laparotomy is considered to be the treatment of choice in most cases. This report deals with a patient who visited our hospital complaining of abdominal pain after colonoscopic polypectomy. The patient was diagnosed with colonic intussusception. After a conservative treatment regimen including antibiotics and fluid therapy, the intussusception was spontaneously reduced.