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Background: Most knowledge on cough epidemiology was obtained from questionnaire surveys of general populations or small focused studies of patients visiting specialist clinics. Routinely collected data (RCD) from electronic health records (EHR) are useful sources for studying disease epidemiology, but their use was limited in chronic cough. The present study aimed to investigate cough presentation and cough-related healthcare utilization, using the RCD of patients referred with cough.Methods: This is a retrospective cohort study utilizing an academic institutional EHR database. Cough cases were identified using the text search for the chief complaint indicating “cough” in the structured case report form. Using the information, we constructed a retrospective cohort of patients with subacute or chronic cough. Baseline demographics, medical history, concomitant symptoms, and diagnostic tests were analyzed. Healthcare utilization during 1 year since the baseline visit was assessed for drug prescriptions, additional diagnostic tests, outpatient visits, and hospitalization.Results: Among a total of 28,312 new referrals, cough was the chief complaint in 13,223 cases (46.7%). Based on the selection criteria, 3,810 subacute and 7,150 chronic cough patients were finally included. A common demographic profile was middle-aged woman (mean age 52.1 years, and female 63%). Patients had a median three accompanying symptoms (interquartile range: 2–5). Abnormal throat sensation (globus, tickling, or dryness) was the most common (about 70%), but symptoms suggesting nasal diseases, asthma, or acid reflux were also frequent. During the first year, both of subacute and chronic cough patients required multiple drug prescriptions, diagnostic tests, and outpatient visits, but the degree of utilization was higher in patients with chronic cough. Codeine-containing drugs were given to 21.5% of patients with chronic cough, and oral antibiotics to 23.7% and oral steroids to 9.9%.Conclusions: Cough is a common chief complaint among new referrals to tertiary specialist clinics. Cough is accompanied by multiple symptoms and is associated with healthcare utilization, particularly more in patients with chronic cough. Further studies are needed to understand their long-term health outcomes and reduce the disease burden.

Few studies have investigated the relationship between asthma and sarcopenia. We aimed to examine the relationship between asthma and sarcopenia in a community-dwelling geriatric population, especially regarding lung function and asthma control.A cross-sectional dataset from the Korean National Health and Nutrition Examination Survey 2008-2011 was utilized. Data regarding asthma history, age at asthma onset, recent asthma exacerbations, and hospitalization for asthma exacerbations were obtained using structured questionnaires. Appendicular skeletal muscle was calculated as the sum of the skeletal muscle mass, and physical activity was assessed using the International Physical Activity Questionnaire.Asthma presented an estimated incidence of 6.17 ± 0.37% in the elderly. Groups were divided and analyzed according to asthma, muscle mass, and physical activity. Sarcopenia was associated with aging, male sex, smoking history, low body mass index (BMI), and reduced lung function with or without asthma. Sarcopenic asthma had a younger onset and reduced physical activity than non-sarcopenic asthma. Obstructive patterns were more frequent in asthmatics exhibiting low or moderate physical activity levels than in those with high activity, but asthma control was not associated with sarcopenia and physical activity. Multivariate logistic regression analyses showed that compared with control, sarcopenic asthma was associated with FEV1 60%, and airway obstruction, and with aging, male, and lower BMI, compared with non-sarcopenic asthma.Our findings suggest that decreased muscle mass and physical activity levels contribute to reduced lung function in elderly asthmatics. Furthermore, sarcopenic asthma was associated with aging, low BMI, and reduced lung function in the elderly.

Asthma is a chronic eosinophilic inflammatory disease with an increasing prevalence worldwide. Endocannabinoids are known to have immunomodulatory biological effects. However, the contribution of oleoylethanolamide (OEA) to airway inflammation remains to be elucidated. To investigate the effect of OEA, the expression of proinflammatory cytokines was measured by RT-qPCR and ELISA in airway epithelial (A549) cells. The numbers of airway inflammatory cells and cytokine levels in bronchoalveolar lavage fluid, airway hyperresponsiveness, and type 2 innate lymphoid cells (ILC2s) were examined in BALB/c mice after 4 days of OEA treatment. Furthermore, eosinophil activation after OEA treatment was evaluated by measuring cellular CD69 levels in eosinophils from human peripheral eosinophils using flow cytometry. OEA induced type 2 inflammatory responses in vitro and in vivo. OEA increased the levels of proinflammatory cytokines, such as IL-6, IL-8, and IL-33, in A549 cells. In addition, it also induced eosinophilic inflammation, the production of IL-4, IL-5, IL-13, and IL-33 in bronchoalveolar lavage fluid, and airway hyperresponsiveness. OEA increased the numbers of IL-5- or IL-13-producing ILC2s in a mouse model. Finally, we confirmed that OEA increased CD69 expression (an eosinophil activation marker) on purified eosinophils from patients with asthma compared to those from healthy controls. OEA may play a role in the pathogenesis of asthma by activating ILC2s and eosinophils., Asthma: A physiological cannabinoid promotes inflammation Oleoylethanolamide (OEA), an endocannabinoid similar to those found in cannabis, occurs naturally in the body, and has now been implicated in promoting symptoms of asthma. OEA activates white blood cells called eosinophils and ILC2 cells, which are both parts of our immune response. Researchers in South Korea, led by Ga-Young Ban at Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, studied the effect of OEA on respiratory system cells from people with asthma and in mice used to model the condition in humans. OEA-induced inflammatory responses associated with asthma by stimulating the release of signaling molecules called cytokines. However, some other endocannabinoids have anti-inflammatory effects. Studying the effects of all endocannabinoids could yield new insights into asthma, with this study opening new possibilities for treating asthma by interfering with OEA-induced signaling responses.

Background There is very limited evidence regarding long-term prognosis of chronic cough. We examined longitudinal outcomes among patients with chronic cough, and explored predictors of cough persistence. Methods A retrospective cohort was constructed of adults who had newly visited a specialist cough clinic in 2012–2013. All had undergone systematic investigation for chronic cough. The Hull Airway Reflux Questionnaire (HARQ) was administered to assess reflux cough symptoms. A follow-up survey was conducted in 2016–2017 to assess cough persistence. Results From 418 candidates, 323 participated in the follow-up study; main analyses focused on patients with chronic persistent cough (n = 64; 19.8%) and remitted cough (n = 193; 59.8%). Compared with remitted cough group, chronic persistent cough group had more family history of chronic cough (17.2% vs. 4.7%, p = 0.001) and cold air-sensitive cough (62.5% vs. 44.6%, p = 0.013). The total HARQ score did not differ; however, two items (cough with eating and cough with certain foods) scored significantly higher in chronic persistent cough. In multivariate analyses, a family history of chronic cough (adjusted odds ratio 4.27 [95% confidence interval 1.35–9.89]), cold air-sensitive cough (2.01 [1.09–3.73]), and cough with eating (1.22 [1.02–1.45]) were associated with chronic persistent cough at 4 years. Conclusions Cough persists in about 20% of patients after 4 years following systematic assessment and treatments. Several cough characteristics, such as family history, cold air-sensitivity, or reflux cough, may be associated with cough persistence. Larger cohort studies are warranted to further understand long-term prognosis and confirm predictors of persistence in patients with chronic cough.

Different patterns of bacterial communities have been reported in the airways and gastrointestinal tract of asthmatics when compared to healthy controls. However, the blood microbiome of asthmatics is yet to be investigated. Therefore, we aimed to determine whether a distinct serum microbiome is observed in asthmatics by metagenomic analysis of serum extracellular vesicles (EVs). We obtained serum from 190 adults with asthma and 260 healthy controls, from which EVs were isolated and analyzed. The bacterial composition of asthmatics was significantly different from that of healthy controls. Chao 1 index was significantly higher in the asthma group, while Shannon and Simpson indices were higher in the control group. At the phylum level, Bacteroidetes was more abundant in asthmatics, while Actinobacter, Verrucomicrobia, and Cyanobacteria were more abundant in healthy controls. At the genus level, 24 bacterial genera showed differences in relative abundance between asthmatics and controls, with linear discriminant analysis scores greater than 3. Further, in a diagnostic model based on these differences, a high predictive value with a sensitivity of 0.92 and a specificity of 0.93 was observed. In conclusion, we demonstrated distinct blood microbiome in asthma indicating the role of microbiome as a potential diagnostic marker of asthma.

Background Laryngeal or vocal cord dysfunction has long been regarded as a mimic of asthma; however, recent evidence indicates that it may be a significant comorbid condition in patients with asthma. Objective We aimed to systematically estimate the prevalence of comorbid laryngeal dysfunction (LD) in adults with asthma and characterize its clinical impact on asthma. Methods Electronic databases were searched for relevant studies published until June 2019. Studies were included if LD was objectively defined by direct visualization of laryngeal movement. Outcomes included the prevalence of LD and its association with clinical asthma indicators, such as severity, control, and quality of life. Random effects meta-analyses were performed to calculate the estimates. Results A total of 21 studies involving 1637 patients were identified. Overall, the pooled prevalence of LD in adults with asthma was 25% (95% CI = 15%-37%; I2 = 96%). Prevalence estimates differed according to the diagnostic test utilized, with the lowest overall prevalence (4% [95% CI = 0%-10%; I2 = 90%]) seen when LD was diagnosed by resting laryngoscopy without external stimuli; however, it was much higher when diagnosed by laryngoscopy studies utilizing an external trigger, such as exercise (38% [95% CI = 24%-53%; I2 = 90%]) or in studies using a computed tomography–based diagnostic protocol (36% [95% CI = 24%-49%; I2 = 78%]). Only 7 studies reported the associations between LD and clinical asthma indicators; inconsistencies between studies limited meaningful conclusions. Conclusion LD may be a common comorbidity in asthma, affecting about 25% of adult patients. Further prospective studies are needed to better characterize its clinical impact and the benefits of detecting and managing LD in patients with asthma.

Background Laboratory animal allergy (LAA) has not been sufficiently investigated, although LAA is a relatively common work-related condition and important occupational hazard. Objective This study aimed to evaluate the prevalence of LAA and analyze the diagnostic value of serum specific IgE (sIgE) using the skin prick test (SPT) as a comparative standard. Methods Korean laboratory animal researchers who attended an annual symposium were requested to answer questionnaires regarding demographic characteristics, laboratory animal exposure, and symptoms related to laboratory animal exposure. A total of 213 participants underwent a SPT with mouse and rat epithelial allergen extract. We measured sIgE against rodent urine, epithelium, and serum allergens from 63 participants. SPT outcome served as the comparison method. Results Among 223 participants, 213 had direct/indirect exposure to mice or rats, and 30% and 14% of them complained of allergic symptoms after exposure to mouse and rat, respectively. Sensitization rates were 28% for mouse epithelium and 23% for rat epithelium. Compared to a positive SPT with wheal ≥ 3 mm, presence of sIgE against rodent allergens showed a higher positive predictive value of 87-91% at a cut-off level of 0.35 KUA/L. Agreement between SPT and sIgE test was determined to be fair to moderate. Conclusions Sensitization and allergy to mouse and rat were prevalent among laboratory personnel in Korea. When evaluating cases of potential LAA, the sIgE test can provide added diagnostic value if the skin test is positive. Careful interpretation of two tests is required to accurately diagnose LAA.

Background Hypersensitivity reactions to iodinated contrast media (ICM) is a persistent clinical issue with increased use of computed tomography. With the evidence indicating underlying allergic mechanisms, there have been studies regarding the skin tests using ICM. Objective This study aimed to evaluate the intradermal skin test (IDT) as a tool for preventing recurrent hypersensitivity reactions to ICM in patients with prior reactions to a known culprit agent. Methods Sixty-nine patients who had experienced immediate hypersensitivity reactions to ICM were included in the study. All patients underwent IDT with 7 different ICMs, including the causative ICM. We analyzed clinical data from 38 patients who were reexposed to ICMs, grouped by the IDT results to their original culprit ICM. Results Thirty-eight patients showed positive IDT results to the culprit ICM (CULPRIT+), whereas 31 patients showed negative results (CULPRIT−). Sixteen patients from the CULPRIT+ group and 22 from the CULPRIT− group were subsequently exposed to an ICM. In the CULPRIT+ group, 4 of the 5 patients who were subsequently exposed to an IDT-positive ICM reexperienced hypersensitivity reactions. When patients were exposed to IDT-negative ICM as an alternative, hypersensitivity reactions were not observed. In the CULPRIT− group, IDT-positive ICMs did not provoke hypersensitivity reactions whereas 2 patients using IDT-negative ICMs experienced hypersensitivity reactions. Conclusions When the IDT results are positive for the culprit ICM, additional IDTs with other ICMs are needed to select a safe alternative. If the IDT results are negative against the culprit ICM, further IDTs might not play a role in selecting a safe alternative.

Chronic cough is a common problem in various populations. The present study assessed the impact of cough and unmet needs in Korean patients with chronic cough. This cross-sectional multi-center study enrolled adult patients newly referred to clinic for assessment of chronic cough. A second group of patients with unexplained chronic cough following detailed assessment were recruited for comparison. Patients completed self-reported questionnaires, including cough characteristics, impact of cough on daily life, and unmet needs. A total of 447 subjects were recruited from six referral clinics, including 408 with chronic cough and 39 with unexplained chronic cough. Almost all patients reported that cough impacted their daily lives. Psychosocial impacts were more evident in unexplained cough patients compared to newly referred patients. Approximately 75% of newly referred patients had previously sought medical care for cough on multiple occasions, but the effectiveness of treatment was limited (70.3%) or absent (17.3%). The most frequent unmet need was the ineffectiveness of treatment (49.3%), followed by unclear diagnosis (30.1%). The majority of participants ( > 80%) expressed the need for further information on accessing cough specialists and disease management. The main problem faced by unexplained cough patients was poor cough control despite treatment (64%). Chronic cough has a substantial impact on daily life and is worst in those whose cough remains unexplained following assessment. Ineffectiveness of treatment and unclear diagnosis were major unmet needs. Medical information about chronic cough was also lacking. Improvements in the management of chronic cough patients in Korea are necessary.

Background Nasal symptoms frequently coexist in patients with chronic cough, and non-sedating H1-receptor antihistamines (nsH1RAs) are often prescribed for cough management in several countries. However, recommendations on the use of nsH1RAs vary among chronic cough guidelines. This study aimed to examine the efficacy of nsH1RAs over placebos in adolescents or adults with chronic cough or allergic respiratory conditions that may present as chronic cough. Methods Electronic databases were searched for studies published until November 2020. Randomized placebo-controlled trials of nsH1RAs reporting cough endpoints in adolescents or adults with chronic cough or cough-associated allergic respiratory conditions (allergic rhinitis, allergic asthma, or atopic cough) were included. Results A total of 10 placebo-controlled trials were identified. Three studies (one study each involving allergic rhinitis, allergic rhinitis with comorbid asthma, and atopic cough) described baseline and post-treatment cough scores, and all reported significant improvements in subjective cough scores; however, the magnitude of improvement was greater in the 2 studies of patients with atopic cough (relative improvement in cough frequency score: −36.6 ± 8.4%) or seasonal allergic rhinitis-associated cough (cough frequency score: −44.0 ± 7.3% and cough intensity score: −65.7 ± 8.3%) than in the 1 study of allergic rhinitis patients with comorbid asthma (−4.0 ± 1.3%). Meanwhile, the other 7 trials found conflicting results but lacked information on the baseline cough score and did not use validated cough measurement tools; thus, their clinical relevance could not be determined. Conclusion Despite the widespread use of nsH1RAs in patients with chronic cough, only a few clinical trials examining their benefits on cough outcomes have been conducted. There may be a subgroup of patients, particularly those with seasonal allergic rhinitis-associated cough or atopic cough, whose cough may improve with nsH1RA treatment. However, adequately powered trials with validated cough measurement tools are warranted to confirm the role of nsH1RAs in the management of patients with allergic phenotypes of chronic cough.

Targeted therapies have broadened the available treatment options for patients with severe eosinophilic asthma (SEA). However, differences in the magnitude of treatment responses among patients indicate the presence of various underlying pathophysiological processes and patient subgroups.We aimed to describe the characteristics of SEA and identify its patient subgroups.Clinical data from the Cohort for Reality and Evolution of Adult Asthma in Korea were analyzed. Cluster analysis was performed among those with SEA using 5 variables, namely, prebronchodilator forced expiratory volume in 1 s, body mass index, age at symptom onset, smoking amount, and blood eosinophil counts.Patients with SEA showed prevalent sensitization to aeroallergens, decreased lung function, and poor asthma control status. Cluster analysis revealed 3 distinctive subgroups among patients with SEA. Cluster 1 (n = 177) consisted of patients reporting the lowest blood eosinophils (median, 346.8 cells/μL) and modest severe asthma with preserved lung function during the 12-month treatment period. Cluster 2 (n = 42) predominantly included smoking males with severe persistent airway obstruction and moderate eosinophilia (median, 451.8 cells/μL). Lastly, cluster 3 (n = 95) included patients with the most severe asthma, the highest eosinophil levels (median, 817.5 cells/μL), and good treatment response in terms of improved lung function and control status.Three subgroups were identified in SEA through the cluster analysis. The distinctive features of each cluster may help physicians predict patients who will respond to biologics with greater magnitude of clinical improvement. Further research regarding the underlying pathophysiology and clinical importance of each subgroup is warranted.

Exacerbation is a defining feature of severe asthma, and oral corticosteroids (OCSs) are frequently prescribed to manage exacerbations. This qualitative study was conducted to examine the experience of patients with severe asthma, with a focus on asthma exacerbation and OCS treatment. Adults with severe asthma were recruited from three tertiary hospitals in South Korea. Data were collected through in-depth qualitative interviews. Verbatim transcripts were analysed using Colaizzi's phenomenological method to uncover the meaning of the participants’ experience. Recruitment of participants continued until thematic saturation. 14 patients with severe asthma were recruited. Four theme clusters emerged: 1) experience of asthma exacerbation; 2) impact on life; 3) OCS treatments; and 4) disease perception. The patients experienced severe physical and psychosocial distress from asthma exacerbations, felt helpless due to failed efforts to prevent exacerbation and were living a restricted life due to fear of exacerbation. They feared OCS side-effects but had no other choice than to rely on OCSs because other interventions were ineffective. Most had poor knowledge and understanding of severe asthma and the long-term health consequences. Asthma exacerbation affects wide aspects of life in patients with severe asthma. Several components may underlie reliance on OCSs, including experience of distress during exacerbation, fear of future exacerbation and lack of proper knowledge about the long-term health consequences of severe asthma and OCS treatments. A multi-disciplinary approach is warranted to support the patients and to provide systematic education about the long-term health implications of severe asthma., Exacerbation widely affects the lives of people with severe asthma. Distress during exacerbation and fear of future exacerbations may underlie oral steroid reliance. Systematic patient education is warranted about the long-term health implications. https://bit.ly/3lhsBiN

Background Possible variation in bronchodilator response (BDR) according to age at the diagnosis of adult-onset asthma is unknown. Our aim was to assess if BDR in FEV1 is related to age at diagnosis of adult-onset asthma and how many subjects fulfill the 400 mL criterion of BDR, the suggested cut-off for asthma-like reversibility in asthma-COPD overlap (ACO). Methods A total of 1030 patients with adult-onset asthma were included; 245 from SAAS (Seinäjoki Adult Asthma Study, Finland) and 785 from COREA (Cohort for Reality and Evolution of Adult Asthma in Korea) cohorts. BDR in FEV1 at the diagnosis of asthma was assessed. Patients were divided into groups based on age at asthma diagnosis: Results BDR % in FEV1 did not differ between the groups of different age at asthma diagnosis and no correlation between BDR and age was found. Of patients aged ≥40 years, only 18% (SAAS-cohort) and 5% (COREA-cohort) reached the 400 mL BDR in FEV1. After exclusion of possible ACO patients, the results remained similar. Conclusion By using two large cohorts of steroid-naive patients with asthma, we have shown that BDR at diagnosis of asthma is constant over large age span range, and the limit of 400 mL in BDR in FEV1 is rarely reached. Trial registration Seinäjoki Adult Asthma Study is registered at ClinicalTrials.gov with identifier number NCT02733016.

Background The values of the skin prick test (SPT) and allergen-specific IgE (sIgE) measurement in predicting dog and cat allergies remain unclear. We aimed to evaluate the usefulness of SPT and sIgE measurement in predicting self-reported allergic symptoms during exposure to dogs and cats in Korean adults. Methods A total of 552 participants in a pet exhibition in Korea completed questionnaires regarding exposure to dog or cat and the development of allergic symptoms during exposure. Study participants also underwent SPT using 3 different commercially available reagents, and had their blood drawn for measurement of serum total IgE and dog/cat-dander-IgE using ImmunoCAP®. Results Measurement of sIgE for dog and cat dander allergens provided the highest positive and negative predictive values and sensitivity, but not specificity (58%, 87.2%, 67.9%, and 93.1% for allergic symptoms on dog exposure; 64.7%, 83.2%, 74.8%, and 88.9% for those on cat exposure, respectively), in predicting self-reported allergic symptoms on dog and cat exposure. The sIgE level consistently exhibited the highest area under the receiver operating characteristic curve (0.749 and 0.719 for allergic symptoms on dog and cat exposure, respectively). Careful interpretation of SPT and sIgE measurements maximized the positive and negative predictive values, sensitivity, and specificity for predicting allergic symptoms on dog exposure (71.4%, 87.3%, 75.3%, and 99.3%) and those on cat exposure (71.4%, 85.3%, 79.3%, and 98.9%). Conclusions The measurement of dog and cat dander sIgE levels may be useful for the exclusion of allergic symptoms related to pet exposure. Collective interpretation of SPT and sIgE tests facilitates identification of allergic symptoms on dog or cat exposure, giving a better rule-in test result.

Additional file 1: Table S1. Bronchodilator response (BDR) in FEV1 grouped by age at asthma diagnosis in SAAS cohort after exclusion of ACO patients. Table S2. Bronchodilator response (BDR) in FEV1 grouped by age at asthma diagnosis in COREA cohort after exclusion of ACO patients.

Derangement in bone mineral density (BMD) caused by glucocorticoid is well-known. The present study aimed to find key biological pathways associated with low BMD after glucocorticoid treatment in asthmatics using gene expression profiles of peripheral blood cells. We utilized immortalized B cells (IBCs) from 32 childhood asthmatics after multiple oral glucocorticoid bursts and peripheral blood mononuclear cells (PBMCs) from 17 adult asthmatics after a long-term use of oral glucocorticoid. We searched co-expressed gene modules significantly related with the BMD Z score in childhood asthmatics and tested if these gene modules were preserved and significantly associated with the BMD Z score in adult asthmatics as well. We identified a gene module composed of 199 genes significantly associated with low BMD in both childhood and adult asthmatics. The structure of this module was preserved across gene expression profiles. We found that the cellular metabolic pathway was significantly enriched in this module. Among 18 hub genes in this module, we postulated that 2 genes, CREBBP and EP300, contributed to low BMD following a literature review. A novel biologic pathway identified in this study highlighted a gene module and several genes as playing possible roles in the pathogenesis of glucocorticoid- induced derangement in BMD.

Background: Although several biomarkers have been proposed for allergic asthma, parameters are still controversial as biomarkers to reflect the efficacy of treatment. Mas-related G protein-coupled receptor-X2 (MRGPRX2) is a newly emerging agent in allergic and inflammatory disease. Objective: The aim of this study was to analyze the MRGPRX2 concentrations in asthmatic patients, evaluating its role as a predictor of outcomes in allergic asthma. Methods: We enrolled 102 healthy controls (CON), 164 allergic (AL), and 78 nonallergic asthmatic (NA) patients from the Cohort for Reality and Evolution of adult Asthma in Korea (COREA). We measured MRGPRX2 concentration (ng/ml) using an Enzyme-linked immunosorbent assay(ELISA) kit. Results: The mean serum MRGPRX2 level in the allergic asthma was higher than nonallergic and healthy groups (AL: 102.4 ± 54.5 vs. NA: 79.8 ± 52.5 vs. CON: 12.9 ± 9.8, p Conclusion: Allergic asthmatic patients with MRGPRX2 levels≥100 ng/ml had good response of ICS although they need higher dose of ICS to treatment. This is the first study demonstrating the role of MRGPRX2 as new biomarker to predict treatment dose and response of ICS in allergic asthmatic patients.

Background: To avoid over-diagnosing of asthma-COPD overlap (ACO), a higher cut-off of 400mL for bronchodilator response (BDR) in FEV1 has been proposed for patients with asthma diagnosed at age ≥40 years. However, it is not known how many asthmatics fulfill this criterion and whether BDR is related to age at diagnosis of adult-onset asthma. Aim: To assess if BDR in FEV1 is related to age at diagnosis of adult-onset asthma and how many subjects fulfill the 400 mL criterion of BDR. Methods: 1030 patients with adult-onset asthma (age of onset ≥15 years) were included; 245 from SAAS (Seinajoki Adult Asthma Study) and 785 from COREA (Cohort for Reality and Evolution of Adult Asthma in Korea) cohorts, respectively. The BDR in FEV1 at the diagnosis of asthma was assessed. Patients were divided into groups based on age at asthma diagnosis: Results: BDR % in FEV1 did not differ between the groups with different age at asthma diagnosis. BDR % in FEV1 in age groups of Conclusion: BDR % in FEV1 at the diagnosis of adult-onset asthma does not vary according to age at diagnosis, and the limit of 400mL BDR in FEV1 is rarely reached. Our findings suggest that the cut-off for BDR of 400 mL has a low sensitivity to detect adult-onset asthma.

Chronic rhinosinusitis and nasal polyps (CRSwNP) is a common condition that significantly affects patients’ life. This work aims to provide an up-to-date overview of CRSwNP in older adults, focusing on its aging-related clinical presentations, pathophysiology, and comorbidity associations including asthma. Recent large population-based studies using nasal endoscopy have shown that CRSwNP is a mostly late-onset disease. Age-related changes in physiologic functions, including nasal epithelial barrier dysfunction, may underlie the incidence and different clinical presentations of CRSwNP in older adults. However, there is still a paucity of evidence on the effect of aging on phenotypes and endotypes of CRSwNP. Meanwhile, late-onset asthma is a major comorbid condition in patients with CRSwNP; they frequently present with type 2 inflammatory signatures that are refractory to conventional treatments when they are comorbid. However, as they are more commonly non-atopic, causative factors other than classical atopic sensitization, such as Staphylococcus aureus specific IgE sensitization, are suggested to drive the type 2 inflammation. There are additional comorbidity associations in older patients with CRSwNP, including those with chronic otitis media and head and neck malignancy. Age is a major determinant for the incidence and clinical presentations of CRSwNP. Given the heterogeneity in phenotypes and endotypes, longitudinal investigations are warranted to elucidate the effects of aging on CRSwNP.

PURPOSE The incidence of drug-induced liver injury (DILI) has been increasing; however, few algorithms are available to identify DILI in electronic health records (EHRs). We aimed to identify and evaluate DILI with an appropriate screening algorithm. METHODS We collected data from 3 university hospitals between June 2015 and May 2016 using our newly developed algorithm for identifying DILI. Among patients with alanine transferase (ALT) ≤ 120 IU/L and total bilirubin (TB) ≤ 2.4 mg/dL in blood test results within 48 hours of admission, those who either had 1) ALT > 120 IU/L and TB > 2.4 mg/dL or 2) ALT > 200 IU/L at least once during hospitalization were identified. After excluding patients with liver disease-related diagnosis at discharge, medical records were retrospectively reviewed to evaluate epidemiological characteristics of DILI. RESULTS The total number of inpatients was 256,598, of whom 1,100 (0.43%) were selected by the algorithm as suspected DILI. Subsequently, 365 cases (0.14% of total inpatients, 95% confidence interval, 0.13-0.16) were identified as DILI, yielding a positive predictive value of 33.1%. Antibiotics (n = 214, 47.2%) were the major class of causative drug followed by chemotherapeutic agents (n = 87, 19.2%). The most common causative drug was piperacillin-tazobactam (n = 38, 8.4%); the incidence of DILI by individual agent was highest for methotrexate (19.4 cases/1,000 patients administered the drug). Common reasons for excluding suspected DILI cases were ischemic hepatitis and postoperative liver dysfunction. CONCLUSIONS Using our EHR-based algorithm, we identified that approximately 0.14% of patients developed DILI during hospitalization. Further studies are needed to modify criteria for more accurate identification of DILI.

Background The number of hypersensitivity reactions associated with iodinated contrast media (ICM) is increasing with widespread use of radiographic contrast agents. These hypersensitivity reactions are unpredictable and sometimes lead to severe reactions such as anaphylaxis. Objective To investigate the value of intradermal skin test (IDT) as a clinical screening tool for prediction of a hypersensitivity reaction to ICM. Methods We performed IDT in the patients scheduled to receive an iodinated contrast agent between September 2015 and April 2017. After IDT, the contrast agent tested was administered intravenously, regardless of the results of skin testing, and the patients were carefully monitored. Results We recruited 2,918 patients in 2 hospitals, and 2,843 were included in the final analysis. Fifteen (0.5%) of the 2843 patients had a positive IDT result before scheduled computed tomography scan; however, none of these patients experienced a hypersensitivity reaction after the administration of a full dose of ICM. Meanwhile, 19 patients who experienced hypersensitivity reactions after ICM challenge had showed a negative IDT result. The sensitivity and the positive predictive value of IDT for ICM were both 0%. Conclusions Routine IDT before the administration of an iodinated contrast agent does not predict hypersensitivity considering its extremely low sensitivity and a low positive predictive value.

Chronic cough is a multi-factorial syndrome commonly presenting as cough hypersensitivity in adult patients. It is a common medical condition in the communities but is more prevalent in older adults. Elderly patients (≥65 years) frequently suffer from multiple comorbidities, which may lead to more clinical heterogeneity in chronic cough and pose diagnostic and therapeutic challenges. Hyposensitivity in cough reflex, probably resulting from central nervous system illnesses, is another potential concern. Despite these complexities and challenges, elderly-specific issues have rarely been addressed in current clinical practice guidelines for chronic cough. Considering recent trends in global population aging, the burden of elderly chronic cough is expected to increase into the near future. This review aimed to respond to following clinical questions: (1) is chronic cough a more heterogeneous condition in the elderly compared to younger adults; and (2) are there additional considerations when choosing the diagnostic and therapeutic approaches to this condition in the elderly?

Cough is an important physiological mechanism to protect the lower airways, but it is also one of the most common symptoms that lead patients to seek medical consultations. Chronic cough, usually defined by cough duration longer than 8 weeks in adults, is prevalent in the community and impairs quality of life in individual patients. There are several characteristics that may differentiate pathologic coughs from protective cough responses, including cough duration, frequency, hypersensitivity, impaired cough suppressibility, or treatment refractoriness. However, the impact of cough, or its perceived severity, is a sum of the patient's experience of coughing and is a factor that may finally define cough as a disease. Social isolation is a major impact of chronic cough, which is now worse due to the coronavirus disease 2019 pandemic and a widespread fear of cough as a source of contagion. Emotional impact and economic impact (medical cost, reduced work productivity, and job loss) are also important complications of chronic cough, and they interact in a vicious cycle, aggravated by social isolation and treatment failures. This paper is a narrative review that aims to address the impact and disease burden of chronic cough in adult patients. We review the literature, but also introduce the findings from recent qualitative interviews and the patients' experiences of the impact and burden of chronic cough and discuss unmet needs in these patients.

Severe asthma (SA) presents in about 3%-5% of adult asthmatics and is responsible for over 60% of asthma-related medical expenses, posing a heavy socioeconomic burden. However, to date, a precise definition of or clear diagnostic criteria for SA have not been established, and therefore, it has been challenging for clinicians to diagnose and treat this disease. Currently, novel biologics targeting several molecules, such as immunoglobulin E, interleukin (IL)5, and IL4/IL13, have emerged, and many new drugs are under development. These have brought a paradigm shift in understanding the mechanism of SA and have also provided new treatment options. However, we need to agree on a precise definition of and its diagnostic criteria for SA. Additionally, it is necessary to explain the diagnostic criteria and to summarize current standard and additional treatment options. This review is an experts' opinion on SA from the Korean Academy of Asthma, Allergy, and Clinical Immunology, the Working Group on Severe Asthma, and aims to provide a definition of and diagnostic criteria for SA, and propose future direction for SA diagnosis and management in Korea.

Purpose Chronic cough is a prevalent condition in the community and may pose considerable impairment to quality of life (QoL). However, its disease burden remains largely undefined in the general population. The present study investigated the relationship between chronic cough and health-related QoL in a Korean nationwide population database, with an emphasis on clinical conditions which may confound the impact of cough. Methods This study analyzed cross-sectional datasets of adults (aged ≥ 40 years) in the Korean National Health and Nutrition Examination Survey 2010–2016. Health-related QoL was assessed using the 3-level EuroQoL 5-dimension component (EQ-5D-3L) index score. The presence of chronic cough and other conditions were defined using structured questionnaires. Results The prevalence of chronic cough was 3.48% ± 0.17% among adults aged ≥ 40 years. The overall EQ-5D-3L index score was significantly lower in subjects with than without chronic cough (0.79 ± 0.01 vs. 0.86 ± 0.00, P < 0.001). In subgroup analyses by age and sex, chronic cough had a notably large impact on QoL in women aged ≥ 65 years (vs. those without chronic cough: 0.55 ± 0.04 vs. 0.70 ± 0.01, P < 0.001), although the mean difference in the scores exceeded the minimally important difference score of 0.05 in all subgroups. In multivariate analyses, chronic cough was significantly associated with QoL, independent of confounders including depression, arthritis, asthma, and chronic obstructive pulmonary disease. In dimension analyses, chronic cough was more associated with anxiety/depression, pain/discomfort, and usual activities than with self-care or mobility in the EQ-5D. Conclusions The present study demonstrated significant associations between chronic cough and health-related QoL in a nationwide large general adult population aged ≥ 40 years, which were independent of clinical confounders. The impact of chronic cough was greater in women aged ≥ 65 years. These findings indicate a considerable burden of chronic cough in the general population and warrant further investigations to assess the disease burden of chronic cough in a global scale.

The various adverse drug reactions (ADRs) arise from different types of iodinated contrast media (ICM).Thus, we investigated the occurrence rate and types of ADRs according to the total usage cases of the 7 most common ICM.We retrospectively reviewed 74,242 causal ADRs caused by ICM from the Korea Adverse Event Reporting System database between January 2014 and December 2016. The 11,712,796 total usage cases that represent all administrations of ICM reported from individual medical institutions were received from the Health Insurance Review and Assessment Service. A proportionality test was used to examine the differences in the frequency ratio of causal ADRs to total usage cases.Immediate hypersensitivity (44,467 cases, 88.56%) occurred more frequently than delayed hypersensitivity (5,725 cases, 11.4%; P.001). The overall occurrence rate of causal ADRs and serious ADRs considering total usage cases was 0.37% and 0.02%, respectively (P.001). The ICM most commonly resulting in ADRs were iomeprol (0.7%) and iopromide (0.59%). The serious ADRs were most common for iomeprol (0.05%). When ADRs were classified according to the system organ class, "skin and appendages disorders" (47,065 cases, 63.4%) occurred most common. Iodixanol resulted in the highest frequency of "urinary system disorders."By comparison of the ADRs considering total usage cases, the incidence and classification of ADRs were different for each contrast medium. A prospective study is needed because the differences in these 7 major contrast media may assist in the selection of ICM tailored for each patient.

Background Chronic rhinosinusitis (CRS) is a major disease condition with high morbidity and can influence lower airway disease status in adults. However, its associations with adult asthma onset and activity have not been examined in detail in a general adult population. Objective To investigate relationships between CRS with nasal polyps (CRSwNP) and asthma characteristics. Methods A cross-sectional data set of 17,506 adult participants (≥18 years old) in the Korean National Health and Nutrition Examination Survey from 2010 through 2012 was analyzed. CRS was defined using structured questionnaires according to the international guideline, and presence of nasal polyps was objectively assessed using nasal endoscopy. Presence of asthma and its onset and current activity were assessed using structured questionnaires. Results CRS was significantly related to asthma, but the relationships were distinct by CRS and asthma status. CRSwNP was significantly associated with adult-onset asthma (onset after 18 years of age) or late-onset asthma (onset after 40 years of age), whereas CRS without nasal polyps was related to childhood-onset asthma (onset before 18 years) or early-onset asthma (onset before 40 years) in adults. The 2 CRS subgroups showed significant associations with current asthma but not with past asthma. However, the comorbid asthma rate was lower than 10% among subjects with CRS. Conclusion This study found distinct age-related patterns of CRSwNP and asthma and demonstrated their significant associations in a general population. However, the low prevalence of asthma in CRSwNP is in sharp contrast to findings in Western populations, which warrants further investigation for ethnic or regional differences in relationships between CRSwNP and asthma.

Background: Upper airway diseases have been considered as potential risk factors of lower airway obstruction. However, their relationships have rarely been examined in general population samples. Objective: To investigate the relationships between lower airway obstruction and upper airway diseases, particularly chronic rhinosinusitis with nasal polyps. Methods: We analyzed cross-sectional data which were collected from 9,369 adult participants in the Korean National Health and Nutrition Examination Survey 2010-2012. The presence of nasal polyps was objectively assessed by nasal endoscope. Chronic nasal symptoms and ever asthma were defined using structured questionnaires. Lower airway obstruction was defined as FEV1/FVC ratio Results: In univariate analyses, lower airway obstruction was significantly related to older age, smoking status, ever asthma, or nasal polyps. Among four symptoms of chronic rhinosinusitis, only 9reduction or loss of smell9 was significantly associated with lower airway obstruction. In multivariate analyses, the significance of relationships between lower airway obstruction and nasal polyps were independent of age, ever asthma or 9reduction or loss of smell9; however, they were significantly affected by smoking status. Meanwhile, the relationships between lower airway obstruction and anosmia were independent of smoking status and ever asthma, but dependent on age. Conclusions: Smoking may be a confounder of the relationships between nasal polyps and lower airway obstruction in a general population samples. However, considering the heterogeneity of nasal polyps, phenotype investigation is warranted.

We report on a first case of bone marrow metastasis by dedifferentiated liposarcoma. A 39-year-old male diagnosed with retroperitoneal dedifferentiated liposarcoma underwent surgery and postoperative radiotherapy. In spite of radiotherapy, his whole-body positron emission tomography showed high uptake in multiple bone metastasis. With thrombocytopenia, bone scan suggested bone marrow involvement. After bone marrow biopsy, bone marrow metastasis by dedifferentiated liposarcoma was finally confirmed. He was administered with systemic chemotherapy with doxorubicin. But he died 3 months after chemotherapy due to disease progression. This case revealed that in a patient of unexplained cytopenia with dedifferentiated liposarcoma, bone marrow metastasis should be in consideration.

Lamotrigine is a recent medication which is prescribed for various neuropsychiatric conditions. It is generally well-tolerated, but recent pharmacoepidemiological evidence suggests that lamotrigine is associated with risks of developing severe cutaneous drug reactions like toxic epidermal necrolysis (TEN). However, there still remains the diagnostic challenge regarding how to confirm the drug causality in suspected cases. In most cases so far, lamotrigine causality has not been objectively demonstrated, which was possibly due to high risk of oral challenge tests or the lack of useful in vitro drug assays. Here we report a case of lamotrigine-induced TEN, of which the drug causality was confirmed by in vitro granulysin and cytokine assays.

Background Severe hypersensitivity reactions (HSRs) interfere with the administration of necessary drugs for patients; drug desensitization can be a good alternative strategy. Although rapid drug desensitization (RDD) has been shown to be safe and effective, some patients still experience breakthrough reactions (BTRs) during desensitization. Objective We aimed to estimate clinical outcomes of RDD and to identify risk factors for BTR. Methods From January 2015 to December 2017, retrospective analysis was done in cancer patients with HSRs to chemotherapy and monoclonal antibody who underwent 3-bag, 12-step RDD in Asan Medical Center. Results A total of 58 patients (42 females; mean age, 54.7 ± 11.0) underwent 234 desensitization procedures. The most common underlying malignancy was gynecologic cancer (n = 26, 44.8%), and platinum-based drugs were common target drugs (135 cases of 36 patients). Twenty-six of 58 patients (44.8%) experienced 56 BTRs, whereas 178 cases (76.1%) of total desensitization did not show any reactions. Among them, 12 patients (20.7%) had moderate BTRs requiring systemic steroids, and 3 (5.1%) experienced severe BTRs requiring epinephrine administration. Logistic regression analysis revealed more severe initial HSRs (OR = 17.94, 95% CI = 1.78-181.68, P = .015), drug allergy history (OR = 7.83, 95% CI = 1.48-41.44, P = .035), and frequency of exposure to the chemotherapeutic agents (OR = 1.14, 95% CI = 1.01-1.28, P = .016) increased the risk of moderate to severe BTR. Conclusion The standardized 12-step protocol for RDD was effective and safe for most patients. Severity of initial HSR, history of drug allergy, and previous high exposure to the chemotherapeutic agent showed a positive correlation with BTR above moderate grade. Studies are needed to propose an individualized protocol according to patient-specific risk assessment.

Background Staphylococcus aureus (SA) is a frequent colonizer in humans, and it is known to be associated with chronic allergic diseases including asthma. Recent individual studies suggested that nasal SA colonization may be positively associated with asthma. Objective To examine relationships between nasal SA colonization and asthma prevalence and activity in adults. Methods Electronic databases were searched for studies published until June 2018. Studies that reported nasal SA colonization prevalence and asthma outcome (prevalence and disease activity) in general adult populations or patients with chronic rhinosinusitis (CRS) were included. Random effects meta-analyses were performed to calculate pooled odds ratio (OR) of the relationships. Subgroup analysis was conducted for the presence of nasal polyps within CRS populations. Results A total of 21 cross-sectional studies were identified, and the data from 16 studies using culture methods for SA detection were meta-analyzed (5 general population-based studies and 11 studies of patients with CRS). In studies of general populations, nasal SA colonization had significant relationships with asthma prevalence (OR 1.19; 95% confidence interval [CI] 1.06-1.34; I2 = 1%). In studies of patients with CRS, positive associations were also found but had a considerable heterogeneity (OR 1.87; 95% CI 1.18-2.97; I2 = 72%). However, the results were comparable between CRS with and without nasal polyps. Conclusions This study demonstrated modest but significant relationships between nasal SA colonization and asthma, supporting potential roles of SA in adult patients with asthma. Further longitudinal cohort and intervention studies are warranted to identify host determinants and to clarify causality of the relationships.

Purpose Recent evidence suggests that cough hypersensitivity may be a common feature of chronic cough in adults. However, the clinical relevance remains unclear. This study evaluated the cough-related symptom profile and the clinical relevance and impact of cough hypersensitivity in adults with chronic cough. Methods This cross-sectional multi-center study compared cough-related laryngeal sensations and cough triggers in patients with unexplained chronic cough following investigations and in unselected patients newly referred for chronic cough. A structured questionnaire was used to assess abnormal laryngeal sensations and cough triggers. Patients with unexplained cough were also evaluated using the Leicester Cough Questionnaire (LCQ) and a cough visual analogue scale (VAS), and these scores were assessed for correlations with the number of triggers and laryngeal sensations. Results This study recruited 478 patients, including 62 with unexplained chronic cough and 416 with chronic cough. Most participants reported abnormal laryngeal sensations and cough triggers. Laryngeal sensations (4.4 ± 1.5 vs. 3.9 ± 1.9; P = 0.049) and cough triggers (6.9 ± 2.6 vs. 5.0 ± 2.8; P < 0.001) were more frequent in patients with unexplained chronic cough than in those with chronic cough. The number of triggers and laryngeal sensations score significantly correlated with LCQ (r = −0.51, P < 0.001) and cough VAS score (r = 0.53, P < 0.001) in patients with unexplained chronic cough. Conclusions Cough hypersensitivity may be a common feature in adult patients with chronic cough, especially those with unexplained chronic cough. Cough-related health status and cough severity were inversely associated with the number of triggers and laryngeal sensations, suggesting potential relevance of assessing cough hypersensitivity in chronic cough patients.