Work-related asthma in adults with severe asthma from the Korean Severe Asthma Registry (KoSAR).

Background: Exposure to allergens or irritants in the workplace may affect asthma control and the quality of life (QoL) of patients with asthma. Objective: To examine the prevalence and characteristics of work-related asthma (WRA) in adult patients with severe asthma. Methods: We analyzed data from the Korean Severe Asthma Registry (KoSAR), which is a nationwide multicenter observational study on severe asthma in Korea. Severe asthma was defined according to the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. WRA was identified on the basis of asthma symptom aggravation at the workplace, as indicated by responses to a structured questionnaire. We compared the demographic and clinical characteristics and QoL between adult patients with severe asthma and WRA and those without WRA. Results: Among 364 patients with severe asthma who were employed at the time of enrollment, 65 (17.9%) had WRA. There were no significant differences in age, sex, obesity, or smoking history between the WRA and non-WRA groups. However, individuals with WRA exhibited a higher prevalence of anxiety (7.7% vs 2.4%, P = 0.046) and depression (12.3% vs 3.7%, P = 0.010) than those without. The levels of asthma control, lung function, and frequency of asthma exacerbations were similar between the two groups, but patients with WRA reported lower QoL, as determined by the Quality of Life Questionnaire for Adult Korean Asthmatics (56.6 ± 14.6 vs. 63.5 ± 13.9, P < 0.001). Conclusion: Patients with severe asthma and WRA are more likely to experience anxiety and depression and have lower QoL than those without WRA.

KAAACI Allergic Rhinitis Guidelines: Part 2. Update in Non-pharmacological Management.

Allergic rhinitis is the most common chronic disease worldwide. Various upper airway symptoms lower quality of life, and due to the recurrent symptoms, multiple treatments are usually attempted rather than one definitive treatment. There are alternatives to medical (medication-based) and non-medical treatments. A guideline is needed to understand allergic rhinitis and develop an appropriate treatment plan. We have developed guidelines for medical treatment based on previous reports. The current guidelines herein are associated with the "KAAACI Evidence-Based Guidelines for Allergic Rhinitis in Korea, Part 1: Update in pharmacotherapy" in which we aimed to provide evidence-based recommendations for the medical treatment of allergic rhinitis. Part 2 focuses on non-pharmacological management, including allergen-specific immunotherapy, subcutaneous or sublingual immunotherapy, nasal saline irrigation, environmental management strategies, companion animal management, and nasal turbinate surgery. The evidence to support the treatment efficacy, safety, and selection has been systematically reviewed. However, larger controlled studies are needed to elevate the level of evidence to select rational non-medical therapeutic options for patients with allergic rhinitis.

Intravenous Mesenchymal Stem Cell Administration Modulates Monocytes/Macrophages and Ameliorates Asthmatic Airway Inflammation in a Murine Asthma Model.

Although asthma is a common chronic airway disease that responds well to anti-inflammatory agents, some patients with asthma are unresponsive to conventional treatment. Mesenchymal stem cells (MSCs) have therapeutic potential for the treatment of inflammatory diseases owing to their immunomodulatory properties. However, the target cells of MSCs are not yet clearly known. This study aimed to determine the effect of human umbilical cord-derived MSCs (hUC-MSCs) on asthmatic lungs by modulating innate immune cells and effector T cells using a murine asthmatic model. Intravenously administered hUC-MSCs reduced airway resistance, mucus production, and inflammation in the murine asthma model. hUC-MSCs attenuated not only T helper (Th) 2 cells and Th17 cells but also augmented regulatory T cells (Tregs). As for innate lymphoid cells (ILC), hUC-MSCs effectively suppressed ILC2s by downregulating master regulators of ILC2s, such as Gata3 and Tcf7. Finally, regarding lung macrophages, hUC-MSCs reduced the total number of macrophages, particularly the proportion of the enhanced monocyte-derived macrophage population. In a closer examination of monocyte-derived macrophages, hUC-MSCs reduced the M2a and M2c populations. In conclusion, hUC-MSCs can be considered as a potential anti- asthmatic treatment given their therapeutic effect on the asthmatic airway inflammation in a murine asthma model by modulating innate immune cells, such as ILC2s, M2a, and M2c macrophages, as well as affecting Tregs and effector T cells.

Desensitization for the prevention of drug hypersensitivity reactions.

Drug desensitization is the temporary induction of tolerance to a sensitized drug by administering slow increments of the drug, starting from a very small amount to a full therapeutic dose. It can be used as a therapeutic strategy for patients with drug hypersensitivity when no comparable alternatives are available. Desensitization has been recommended for immunoglobulin E (IgE)-mediated immediate hypersensitivity; however, its indications have recently been expanded to include non-IgE-mediated, non-immunological, or delayed T cell-mediated reactions. Currently, the mechanism of desensitization is not fully understood. However, the attenuation of various intracellular signals in target cells is an area of active research, such as high-affinity IgE receptor (FcεRI) internalization, anti-drug IgG4 blocking antibody, altered signaling pathways in mast cells and basophils, and reduced Ca2+ influx. Agents commonly requiring desensitization include antineoplastic agents, antibiotics, antituberculous agents, and aspirin/nonsteroidal antiinflammatory drugs. Various desensitization protocols (rapid or slow, multi-bag or one-bag, with different target doses) have been proposed for each drug. An appropriate protocol should be selected with the appropriate concentration, dosage, dosing interval, and route of administration. In addition, the protocol should be adjusted with consideration of the severity of the initial reaction, the characteristics of the drug itself, as well as the frequency, pattern, and degree of breakthrough reactions.

A new non-dilution rapid desensitization protocol successfully applied to all-grade platinum hypersensitivity.

PURPOSE: Desensitization is a safe alternative for patients with hypersensitivity reactions (HSRs) to platinum-based chemotherapeutic agents and widely used in real practice by employing stepwise administration of multiple serial dilutions of the culprit drugs. However, its labor-intensive nature has required a simpler protocol that is easier to prepare and perform. METHODS: We performed an observational study of patients with platinum HSR who underwent a new non-dilution one-bag desensitization protocol. Premedication consisted of Montelukast as well as H1 and H2 blockers. The outcomes and safety profiles of a new protocol were assessed. RESULTS: A total of 36 patients were recruited (oxaliplatin 23, carboplatin 9, and cisplatin 4) and the most common grade of HSR presented was grade 2 (61.1%), followed by grade 3 (25%), and grade 1 (13.9%). Of 175 desensitization procedures, all cases were successfully completed in re-administration of culprit chemotherapeutic platinum agents; 146 (83.4%) had no breakthrough reactions (BTRs) while 29 (16.6%) did. Most BTRs were mild reactions (grade 1, 51.7%) or moderate reactions (grade 2, 44.8%) of Brown's Scale. Although there was one case of asymptomatic mild hypotension (grade 3, 3.5%), categorized as severe reaction, dyspnea, desaturation, and anaphylaxis did not occur. The proportion of severe HSRs was significantly lower than that of initial HSRs (3.5% vs. 25%, P = 0.0167). CONCLUSIONS: The new non-dilution desensitization protocol was safe and effective for re-administration of culprit platinum agents in patients with a history of HSRs. Therefore, this new protocol can be used as an alternative to existing protocols using multiple serial dilutions.

Point prevalence and epidemiological characteristics of chronic cough in the general adult population: The Korean National Health and Nutrition Examination Survey 2010-2012.

Cough is frequently self-limiting, but may persist longer in certain individuals. Most of previous studies on the epidemiology of chronic cough have only measured period prevalence, and thus have afforded limited information on the burden and natural course. We aimed to investigate the epidemiology of chronic cough by using a point prevalence measure in a large-scale general population.We analyzed cross-sectional data collected from 18,071 adults who participated in the Korean National Health and Nutrition Examination Survey 2010-2012. Presence and duration of current cough was ascertained by structured questionnaires, and cough was classified into acute (<3 weeks), subacute (3-8 weeks), or chronic cough (≥8 weeks). Demographic and clinical parameters were examined in relation to chronic cough.The point prevalences of acute, subacute, and chronic cough were 2.5 ±â€Š0.2%, 0.8 ±â€Š0.1% and 2.6 ±â€Š0.2%, respectively. The proportion of current cough showed a steep decrease after 1 week of duration. However, 2 peaks in the prevalence of current cough were revealed; cough durations of less than 1 week and longer than 1 year were most common (31.1% and 27.7% of current cough, respectively). Subacute and chronic cough were more prevalent in the elderly (≥65 years); the positive associations with older age were independent of other confounders, including current smoking and comorbidities.This is the first report on the epidemiology of cough using a point prevalence measure in a nationally representative population sample. Our findings indicate a high burden of chronic cough among adults with current cough in the community. The dual-peak of cough duration suggested that the pathophysiology of acute and chronic cough may differ. The preponderance of elderly people in the prevalence of chronic cough warrants further investigation. In addition, more sophistication and validation of tools to define chronic cough will help our understanding of the epidemiology.

Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation.

Human palatine tonsils are oropharyngeal lymphoid tissues containing multiple invaginations (crypts) in which the continuity of the outer surface epithelium is disrupted and the isolated epithelial cells intermingle with other cell types. We now show that primitive epithelial cells detectable in vitro in 2D colony assays and in a 3D culture system are CD44(+)NGFR(+) and present in both surface and crypt regions. Transcriptome analysis indicated a high similarity between CD44(+)NGFR(+) cells in both regions, although those isolated from the crypt contained a higher proportion of the most primitive (holo)clonogenic cells. Lentiviral transduction of CD44(+)NGFR(+) cells from both regions with human papillomavirus 16-encoded E6/E7 prolonged their growth in 2D cultures and caused aberrant differentiation in 3D cultures. Our findings therefore reveal a shared, site-independent, hierarchical organization, differentiation potential, and transcriptional profile of normal human tonsillar epithelial progenitor cells. They also introduce a new model for investigating the mechanisms of their transformation.

Hypersensitivity reactions to oxaliplatin: clinical features and risk factors in Koreans.

BACKGROUND AND AIM: Oxaliplatin hypersensitivity is a well-known adverse reaction but the prevalence varies and data for frequency and clinical features have not been reported for Korea. Here we evaluates the prevalence and risk factors for hypersensitivity reactions to oxaliplatin after chemotherapy. METHODS: Clinical information on all patients treated with oxaliplatin was retrospectively reviewed in electronic medical records between August 2009 and July 2010 in Seoul National University Bundang Hospital. Patients who experienced hypersensitivity reactions to oxaliplatin were compared with those who did not. RESULTS: A total of 393 patients received oxaliplatin, with 42 (10.7%) experiencing hypersensitivity reactions including three cases of anaphylaxis. Median cycle of the first hypersensitivity reaction was 8. Reactions correlated with lower dexamethasone doses. Other variables were not significant. CONCLUSIONS: The prevalence of hypersensitivity reactions was 10.7%, symptoms being mostly mild and cutaneous. Lower dexamethasone doses could be a predictor for hypersensitivity reactions to oxaliplatin.