Kyung-Hwan Lim

Reliability and validity of a Korean version of the Leicester Cough Questionnaire.

Purpose There are no specific tools for measurement of the severity of chronic cough in Korea. We developed a Korean version of the Leicester Cough Questionnaire (LCQ) and tested its scaling and clinical properties. Methods The LCQ was adapted for Korean conditions following a forward-backward translation procedure. All patients referred to chronic cough clinics at 5 university hospitals between May 2011 and October 2013 completed 2 questionnaires, the LCQ and the Short-Form 36 (SF-36), upon presentation and completed the LCQ and the Global Rating of Change (GRC) upon follow-up visits after 2 or 4 weeks. Concurrent validation, internal consistency, repeatability, and responsiveness were determined. Results For the concurrent validation, the correlation coefficients (n=202 patients) between the LCQ and SF-36 varied between 0.42 and 0.58. The internal consistency of the LCQ (n=207) was high for each of the domains with a Cronbachs alpha coefficient of 0.82-0.94. The repeatability of the LCQ in patients with no change in cough (n=23) was high, with intra-class correlation coefficients of 0.66-0.81. Patients who reported an improvement in cough (n=30) on follow-up visits demonstrated significant improvement in each of the domains of the LCQ. Conclusions The Korean version of the LCQ is a valid and reliable questionnaire for measurement of the severity of cough in patients with chronic cough.

Basophil Activation Test with Food Additives in Chronic Urticaria Patients

The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU.

Reduced IRF7 response to rhinovirus unrelated with DNA methylation in peripheral mononuclear cells of adult asthmatics.

Background Human rhinoviruses are the major cause of asthma exacerbation in both children and adults. Recently, impaired antiviral interferon (IFN) response in asthmatics has been indicated as a primary reason of the susceptibility to respiratory virus, but the mechanism of defective IFN production is little understood to date. The expression of IFN regulatory factor 7 (IRF7), a transcriptional factor for virus-induced type I IFN production is known to be regulated epigenetically by DNA methylation. Objective We aimed to investigate the expression of IFN-α, IFN-β, and IRF7 in response to rhinovirus infection in the adult asthmatics and evaluate DNA methylation status of IRF7 gene promotor. Methods Twenty symptomatic adult asthmatics and 10 healthy subjects were enrolled and peripheral blood was collected from each subject. Peripheral blood mononuclear cells (PBMCs) were isolated, cultured, and ex vivo stimulated with rhinovirus-16. The mRNA expressions of IFN-α, IFN-β, and IRF7 were analyzed using real time quantitative polymerase chain reaction. Genomic DNA was isolated from untreated PBMCs and the methylation status of IRF7 gene promotor was investigated using bisulfite pyrosequencing. Results The mean age of asthmatics was 45.4 ± 15.7 years and 40% was male, which were not different with those of control group. Asthmatics showed significantly decreased mRNA expressions (relative expression to beta-actin) of IFN-α and IFN-β compared with normal control. The mRNA expression of IRF7 in the asthmatics was also significantly lower than those in the normal control. No significant difference of DNA methylation was observed between asthmatics and controls in all analyzed positions of IRF7 promotor CpG loci. Conclusion The mRNA expression of type I IFN in response to rhinovirus was impaired in the PBMCs of adult asthmatics. The mRNA expression of IRF7, transcriptional factor inducing type I IFN was also reduced, but not caused by altered DNA methylation in the IRF7 gene promotor.

Korean version of the Cough Symptom Score: clinical utility and validity for chronic cough

Background/Aims The Cough Symptom Score (CSS) is a simple, useful tool for measuring cough severity. However, there is no standard Korean version of the CSS. We developed a Korean version of the CSS and evaluated its clinical utility and validity for assessing chronic cough severity. Methods The CSS was adapted for Korean use following a forward-backward translation procedure. Patients with chronic cough enrolled from five university hospitals were graded using the CSS and a 100-mm linear visual analog scale (VAS) of cough severity at each visit. Patients completed the Leicester Cough Questionnaire (LCQ) upon presentation and completed the LCQ and Global Rating of Change at follow-up visits after 2 to 4 weeks. The concurrent validity, repeatability, and responsiveness of the Korean version of the CSS were determined. Results Correlation coefficients between the CSS and LCQ, and between the CSS and VAS, were –0.66 and 0.52, respectively. There was a weak correlation between the scores for night and day symptoms (r = 0.24, p = 0.0006). The repeatability of the CSS in patients with no change in cough (n = 23) was high (intra-class correlation coefficient, 0.75; 95% confidence interval [CI], 0.51 to 0.88). Patients who reported an improvement in cough (n = 30) at follow-up visits had a significant improvement in the CSS (median, –2; 95% CI, –3 to –1; p = 0.0003). Conclusions The Korean version of the CSS correlated well with other tools for accessing cough severity in chronic cough patients. Therefore, it could be a reliable method for measuring chronic cough severity.

Hypereosinophilia with rash to dobutamine infusion; sulfite hypersensitivity diagnosed by in vitro stimulation assays.

Dobutamine is a widely prescribed form of inotropic support for patients with heart failure, but infusion thereof has been associated with hypersensitivity reactions, namely eosinophilia or eosinophilic myocarditis.1e5 However, it remains unclear whether the true culprit is dobutamine per se or its excipient, sulfite.6,7 We report a case of recurrent hypereosinophilia with a skin rash that developed during dobutamine infusion. We used an in vitro flow cytometric assay to show that the hypersensitivity was attributable to sulfite.

KAAACI Evidence-Based Clinical Practice Guidelines for Chronic Cough in Adults and Children in Korea

Chronic cough is common in the community and causes significant morbidity. Several factors may underlie this problem, but comorbid conditions located at sensory nerve endings that regulate the cough reflex, including rhinitis, rhinosinusitis, asthma, eosinophilic bronchitis, and gastroesophageal reflux disease, are considered important. However, chronic cough is frequently non-specific and accompanied by not easily identifiable causes during the initial evaluation. Therefore, there are unmet needs for developing empirical treatment and practical diagnostic approaches that can be applied in primary clinics. Meanwhile, in referral clinics, a considerable proportion of adult patients with chronic cough are unexplained or refractory to conventional treatment. The present clinical practice guidelines aim to address major clinical questions regarding empirical treatment, practical diagnostic tools for non-specific chronic cough, and available therapeutic options for chronic wet cough in children and unexplained chronic cough in adults in Korea.

Enhanced drug specific CD8+ T cell response at the presence of HHV-6 in DRESS patient: a case report

Background Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening multiorgan systemic reaction tha ti ncludes skin rash, fever, lymphadenopathy, internal organ involvement, and leukocytosis with eosinophilia. Evidence for reactivation of human herpes virus (HHV) 6 has been seen in some DRESS patients. We present a case of allopurinolinduced DRESS syndrome and describe the immune reactions through the identification of proliferation of CD8-positive T lymphocytes against HHV-6 peptides pool (HHV6-U90) by flow cytometry. Case history A 75-year-old man presented with a 10-day history of generalized rash accompanied by high fever, facial edema, hepatitis and azotemia. Prior to the appearance of the rash, the patient had been treated with allopurinol 200 mg/day due to gout for 20 days. Progressive rash, peripheral blood eosinophilia, multiple lymphadenopathy as well as a positive PCR test for HHV-6 were also present. The diagnosis of DRESS was made. The clinical symptoms and laboratory abnormalities were gradually recovered following administration of systemic corticosteroids (methylprednisolone 1 mg/kg). Result Five years after the resolution of symptoms, lymphocyte transformation test was performed but significant lymphocyte proliferation was not observed with allopurinol stimulation itself in vitro. As a next step, CFSE T cell proliferation assays were conducted with the peripheral blood mononuclear cells of the allopurinol-induced DRESS patient and normal control. CD8+ cytotoxic proliferating T cells were not changed with stimulation of allopurinol in both DRESS patient and normal control. However, in DRESS patient, CD8+ cytotoxic proliferating T cell population was increased with stimulation of allopurinol and HHV6-U90 (33.9%iae41.2%). Conclusion