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.

Diagnosis and treatment of hereditary angioedema: An expert opinion

Hereditary angioedema (HAE) is a rare disease, but it severely interrupts daily life activities and can sometimes be life-threatening. Therefore, early diagnosis and prompt treatment of HAE attacks are critical. Physicians should be aware of how to diagnose and manage HAE to prepare not to miss a diagnosis when treating HAE patients. Physicians must also carry out tests to confirm the diagnosis of HAEs caused by C1 inhibitor deficiency (type 1) or C1 inhibitor dysfunction (type 2) in patients with recurrent angioedema. In addition, recent studies revealed another type of HAE which is not related to C1 inhibitor (normal C1 inhibitor HAE). Once HAE is confirmed, patients and their caregivers should be given with short-term and long-term treatment plans to relieve or prevent HAE attacks. HAE requires life-long measures, including psychological support for patients and self-management education.

Interactions between NCR + ILC3s and the Microbiome in the Airways Shape Asthma Severity

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.

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.

Risk Factors for Acute Exacerbations in Elderly Asthma: What Makes Asthma in Older Adults Distinctive?

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.

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.

Patient-Centeredness during In-Depth Consultation in the Outpatient Clinic of a Tertiary Hospital in Korea: Paradigm Shift from Disease to Patient

BACKGROUND: Patient-centered care (PCC) and integrative care approach are widely advocated. However, their implementation usually requires an extended consultation time. Despite significant advances in medical diagnosis and treatment, no studies have examined consultation time and patient centeredness in Korea. METHODS: We conducted a “15-Minute Consultation” for first-time patients in outpatient clinics of 13 departments. A control group was selected from the same physicians' first-time patients, adjusting for age and gender. A total of 275 patients were selected for receiving in-depth consultation and 141 control patients were selected for regular consultation. Data were collected from patients using a questionnaire comprising a patient-centeredness scale and items on potential predictors such as socio-demographic and clinical factors. We also investigated the participating physician's professionalism. RESULTS: As compared to the control group, the in-depth consultation group scored higher on 5 variables associated with PCC, including (patients' perception of) medical professionals, wait and consultation times, treatment, patient advocacy, and patient satisfaction. While 92.4% of patients in the in-depth consultation group reported that the consultation time was sufficient, only 69.0% of those in the control group reported the same (P < 0.01). In the in-depth consultation group, scores on satisfaction level were the highest for the department of internal medicine, followed by departments of surgery and pediatrics. Participating physicians' improved satisfaction following the intervention proved that in-depth consultation facilitated building a rapport with patients. CONCLUSION: This study illustrated that the provision of sufficiently long consultation for serious and rare diseases could improve PCC and physicians' professionalism. Health authorities should reshuffle the healthcare delivery system and provide sufficient consultation time to ensure PCC and medical professionalism.

Chronic cough, not asthma, is associated with depression in the elderly: a community-based population analysis in South Korea

BACKGROUND/AIMS@#Depression and allergic diseases, including asthma, are frequently reported as comorbid conditions. However, their associations have been rarely examined in community-based elderly populations.@*METHODS@#The analyses were performed using the baseline data set of the Korean Longitudinal Study of Health and Aging, which consists of 1,000 elderly participants (aged > 65 years) randomly recruited from an urban community. Depression was assessed using the Geriatric Depression Scale, Center for Epidemiologic Studies Depression Scale, and Hamilton Rating Scale for Depression. Major and minor depressive disorders were diagnosed by psychiatrists. Allergic conditions were assessed using structured questionnaires, lung function, and skin prick test. Quality of life and comorbidities were assessed using structured questionnaires.@*RESULTS@#Prevalence of asthma and major depressive disorder were 5.4% and 5.3%, respectively. The rate of depression was not significantly different between the non-asthmatic and asthmatic groups. No correlation was observed between the scores obtained using the depression scales and self-reported asthma. However, chronic, frequent, and nocturnal cough were significantly associated with depression and scores obtained using the depression scales, which remained significant in multivariate logistic regression analyses (chronic cough: odds ratio [OR], 3.23; 95% confidence interval [CI], 2.57 to 12.74; p = 0.04). Rhinitis was independently associated with high Mini-Mental State Examination scores (OR, 1.11; 95% CI, 1.05 to 1.17; p < 0.001) and low 36-item short-form (OR, 0.96; 95% CI, 0.80 to 0.98; p = 0.002).@*CONCLUSIONS@#Depression may not be significantly associated with asthma and allergic diseases in elderly populations, but cough is a significant factor affecting depression.

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.

Immediate hypersensitivity reaction to steroids: a case report

Steroids are widely used for the treatment of a variety of diseases, including autoimmune and allergic diseases. Immediate hypersensitivity reactions can occur within 1 hour after administration of steroids and are regarded as IgE-mediated hypersensitivity presenting as urticaria, angioedema, bronchospasm, and anaphylaxis. Steroid hypersensitivity is rare, but can be life-threatening. Therefore, it is important to find implicated drugs and to choose safe alternative agents. A 44-year-old female was diagnosed with steroid hypersensitivity after intralesional steroid injection. She underwent a skin prick test and an intradermal test for methylprednisolone, triamcinolone, hydrocortisone, and dexamethasone. The results were positive to triamcinolone and methylprednisolone. The patient was educated to avoid culprit agents in order to prevent recurrence. Herein, we report a rare case of steroid hypersensitivity that showed positive reactions to triamcinolone and methylprednisolone. A review of the literature for steroid hypersensitivity is also provided.

A case series of eperisone-induced immediate hypersensitivity

Eperisone is a widely used muscle relaxant and believed to be relatively free of adverse drug reactions. However, a rare case of fatal anaphylaxis has been reported in the literature. Poor awareness due to its rarity and combined administration with other drugs are the major hurdles in diagnosing eperisone-induced anaphylaxis. We experienced 3 cases of immediate hypersensitivity reaction occurring after eperisone administration. Case 1, a 63-year-old female, was admitted via the Emergency Department with urticaria, generalized erythroderma, sore throat, chest discomfort, and dyspnea within 1 hour after administration of common cold remedy. Case 2, a 58-year-old male, visited our allergy clinic to detect culprit drugs. He experienced itching, urticaria, hypotension for several hours after administration of the pills for back pain in the last 3 years. Case 3, a 58-year-old male developed urticaria and dyspnea after administration of medication for a headache. He also experienced urticaria and facial edema after administration of the common cold remedy. Among the medications, eperisone hydrochloride was proven as the culprit drug and others were excluded through oral provocation tests. We advised them to avoid eperisone and issued drug safety card. Clinicians should be aware that eperisone hydrochloride is a potential culprit agent of fatal anaphylaxis.

Successful sequential desensitization in a patient with drug hypersensitivity to three kinds of antiplatelet agents

Antiplatelet agents, such as aspirin, clopidogrel, and cilostazol, are essential for the treatment and prevention of cardiovascular, cerebrovascular, and peripheral vascular diseases. A 53-year-old male with aspirin hypersensitivity developed dizziness, which was caused by severe stenosis of the left vertebral artery. Clopidogrel was administerted, but discontinued due to generalized urticaria and angioedema. As an alternative drug, cilostazol was administered, but discontinued again because of the same adverse reactions. Desensitization was planned as other alternative antiplatelet agents were not available. Initially, aspirin desensitization was successfully performed. One day after aspirin desensitization, clopidogrel desensitization was sequentially done successfully. After a few months, cilostazole desensitization was performed. During the follow-up period, he had to stop aspirin and cilostazol twice to prevent the risk of bleeding after a procedure and an operation. After discontinuing medicines, sequential desensitization of aspirin and cilostazol was successfully performed. Physicians should be aware that drug hypersensitivity could be induced by various kinds of antiplatelet agents and that desensitization could be the treatment of choice unless alternative medicines are available.

Analysis of clinical characteristics of food-dependent exercise-induced anaphylaxis at a single tertiary hospital

PURPOSE: Food-dependent exercise-induced anaphylaxis (FDEIA) is a rare subtype of food allergy in which both sensitization to food allergen and exercise as a trigger contribute to its development. However, its pathogenesis is still under investigation. This study compared clinical features, the causative foods, and the degree of sensitization to food between FDEIA and food anaphylaxis to characterize FDEIA more clearly. METHODS: We retrospectively reviewed the medical records of patients who were diagnosed with FDEIA (n=89) or food anaphylaxis (n=115) between 2003 and 2015 at Seoul National University Hospital. RESULTS: Subjects with FDEIA more frequently had urticaria than those with food anaphylaxis (88.8% vs. 76.5%, P=0.024). Whereas patients with FDEIA had less laryngeal edema than those with food anaphylaxis (12.4% vs. 30.4%, P=0.02). Wheat (67.4%) was the most common causative food allergen in FDEIA, whereas seafood (40.9%) was the most common culprit food allergen in food anaphylaxis. Also, subjects with FDEIA showed a lower atopic index score than those with food anaphylaxis (0.55±1.07 vs. 1.21±1.82, P=0.006). CONCLUSION: There were significant differences in clinical manifestation, causative food allergens and the degree of sensitization to food between FDEIA and food anaphylaxis.

Intravenous tacrolimus and cyclosporine induced anaphylaxis: what is next?

Tacrolimus and cyclosporine have been used in various formulations, but their hypersensitivity reactions are rare in practice. Castor oil derivatives are nonionic surfactants used in aqueous preparations of hydrophobic active pharmaceutical ingredients. Castor oil derivatives that can be used as additives to tacrolimus and cyclosporine may play a role in the development of hypersensitivity reactions, especially anaphylaxis. Various immunologic and nonimmunologic mechanisms have been implicated in hypersensitivity reactions induced by castor oil derivatives. Physicians should be aware that not only the drug itself, but also its additives or metabolites could induce hypersensitivity reactions. We report a case of anaphylaxis caused by vitamin K (phytonadine), serotonin antagonist (granisetron), intravenous tacrolimus, and cyclosporine. Interestingly, the patient tolerated oral cyclosporine, which did not contain Cremophor EL or polysorbate 80.

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.

Iodinated contrast media-induced fixed drug eruption

Iodinated contrast media (ICM) can cause not only immediate onset hypersensitivity but also delayed onset hypersensitivity. While the most common form of delayed onset hypersensitivity reaction to ICM is exanthematous eruption, fixed drug eruption (FDE) can occur rarely related to ICM. A 70-year-old male with liver cirrhosis and hepatocellular carcinoma repeatedly experienced erythematous patches on his right forearm and hand 6 hours after exposure to iopromide for computed tomography scan. ICM induced FDE was diagnosed clinically. Intradermal test with 6 kinds of ICM (iobitridol, iohexol, iomeprol, iopamidol, iopromide, and iodixanol) was performed and showed the weakest positive reaction to iohexol compared to the others in 48 hours. After changing iopromide to iohexol based on these results, FDE did not recur. We report here a case of iopromide induced FDE which was successfully prevented by changing ICM to iohexol based on intradermal test results.

Sorafenib Induces Delayed-Onset Cutaneous Hypersensitivity: A Case Series

Sorafenib is an oral multikinase inhibitor with clinical activity against hepatocellular carcinoma (HCC) and renal cell carcinoma. Administration of sorafenib carries a variety of adverse cutaneous reactions. Common adverse effects induced by sorafenib include hand-foot skin reactions, facial erythema, splinter subungual hemorrhage, and alopecia. Although erythema multiforme (EM) related to sorafenib has been reported, delayed-type cutaneous hypersensitivity reactions are rare in patients treated with sorafenib and there has been no case of Stevens-Johnson syndrome (SJS) reported so far. We recently experienced 3 cases of delayed-type cutaneous hypersensitivity related to administration of sorafenib. The first case was a 47-year female had targetoid erythematous rashes on her arms 12 days after starting sorafenib for HCC. The rashes spread from the arms to the trunk rapidly except for the hands and feet, and erosive lesions developed in the oral mucosa and lips. She was diagnosed as SJS. The second case was an 81-year-old male had maculopapular eruptions with multiple targetoid lesions on the trunk, arms, and legs 10 days after starting sorafenib for his HCC. There was no evidence of mucosal involvement. He was diagnosed with EM. The last one was a 20-year-old female developed generalized maculopapular eruptions in the whole body 10 days after starting sorafenib for the treatment of HCC. All 3 patients completely recovered after discontinuation of sorafenib.

ERRATUM: Acknowledgments Correction. Iodinated contrast media-induced fixed drug eruption

Acknowledgments section for grant support was misprinted unintentionally.

Clinical features and prognostic factors of Churg-Strauss syndrome

BACKGROUND/AIMS: Churg-Strauss syndrome (CSS) is a rare systemic necrotizing small-vessel vasculitis, with accompanying bronchial asthma, eosinophilia, and eosinophilic infiltration of various tissues. The purposes of our study were to characterize the clinical features of CSS and to identify factors associated with CSS prognosis in Koreans. METHODS: Medical records were reviewed retrospectively for all physician-diagnosed CSS patients in the Seoul National University Hospital between January 1990 and March 2011. RESULTS: Data from 52 CSS patients were analyzed. The respiratory tract was the most commonly involved organ (90.4%). Renal involvement was less frequent in antineutrophilic cytoplasmic antibody (ANCA)(-) patients than in ANCA(+) patients (p = 0.048). Clinical remission occurred in 95.3% of patients, but 16.3% of them relapsed. Patients who maintained remission for more than 6 months were relatively older (median, 51 years) at diagnosis (p = 0.004), had been diagnosed in earlier stages (p = 0.027), showed more frequent respiratory involvement (p = 0.024) and generalized symptoms (p = 0.039), and showed less frequent cutaneous involvement (p = 0.030) than those who did not achieve persistent (> 6 months) remission. Patients who achieved persistent remission also showed higher C-reactive protein (CRP) levels (p = 0.031) than those who did not. CONCLUSIONS: ANCA(-) CSS patients showed less frequent renal involvement. Characteristics of good responders were older age, diagnosis at earlier stages, less cutaneous involvement, more respiratory involvement, high CRP values, and more generalized symptoms.