Role of club cell 16-kDa secretory protein in asthmatic airways.

BACKGROUND: Club cell 16-kDa secretory protein (CC16) is a pneumoprotein and functions as an anti-inflammatory or antioxidant protein. However, altered levels of serum CC16 as well as their effect on airways inflammation have not been fully evaluated. METHODS: We recruited 63 adult asthmatics on maintenance medications and 61 healthy controls (HCs). The asthmatic subjects were divided into two groups according to the result of bronchodilator responsiveness (BDR) test: the present BDR (n = 17) and absent BDR (n = 46) groups. Serum CC16 levels were measured by ELISA. As an in vitro study, the effect of Dermatophagoides pteronyssinus antigen 1 (Der p1) on the production of CC16 in airways epithelial cells (AECs) according to a time-dependent manner was assessed; the effects of CC16 protein on oxidative stress system, airways inflammation and remodelling were tested. RESULTS: Serum CC16 levels showed significantly higher in the asthmatics than in the HCs (p < .001) with a positive correlation with FEV1 % (r = .352, p = .005). The present BDR group had significantly lower levels of serum CC16, FEV1 % and MMEF%, but showed higher level of FeNO than the absent BDR group. Serum CC16 levels (below 496.0 ng/mL) could discriminate the present BDR group from the absent BDR group (area under the curve = 0.74, p = .004). In vitro testing demonstrated that Der p1 exposure significantly induced CC16 release from AECs for 1 h, which was progressively decreased after 6 h and followed by MMP-9 and TIMP-1 production. These findings were associated with oxidant/antioxidant disequilibrium and restored by CC16 treatment (but not dexamethasone). CONCLUSION: Decreased CC16 production contributes to persistent airways inflammation and lung function decline. CC16 may be a potential biomarker for asthmatics with BDR.

Potential Biomarkers for NSAID-Exacerbated Respiratory Disease.

Asthma is a common chronic disease with several variant phenotypes and endotypes. NSAID-exacerbated respiratory disease (NERD) is one such endotype characterized by asthma, chronic rhinosinusitis (CRS) with nasal polyps, and hypersensitivity to aspirin/cyclooxygenase-1 inhibitors. NERD is more associated with severe asthma than other asthma phenotypes. Regarding diagnosis, aspirin challenge tests via the oral or bronchial route are a standard diagnostic method; reliable in vitro diagnostic tests are not available. Recent studies have reported various biomarkers of phenotype, diagnosis, and prognosis. In this review, we summarized the known potential biomarkers of NERD that are distinct from those of aspirin-tolerant asthma. We also provided an overview of the different NERD subgroups.

Subcutaneous Immunotherapy for Allergic Asthma in a Single Center of Korea: Efficacy, Safety, and Clinical Response Predictors.

Allergen-specific immunotherapy is the only causal treatment for allergic diseases. However, the efficacy of immunotherapy may vary around the world due to differences in climate, the nature of aero-allergens and their distribution. The aim of this study was to describe the effects of subcutaneous immunotherapy (SCIT) in Korean adults with allergic asthma (AA). As a retrospective cohort study, we reviewed medical records for 627 patients with AA in Korea who were sensitized to house dust mite (HDM) and/or pollens and who underwent SCIT with aluminum hydroxide adsorbed allergen extract from 2000 to 2012. Rates of remission, defined as no further requirement of maintenance medication, over time were determined by means of life tables and extension of survival analysis. Herein, 627 asthmatic patients achieved remission within a mean of 4.7 ± 0.2 years. The cumulative incidence rates of remission from AA were 86.9% upon treatment with SCIT. Baseline forced expiratory volume in the first second (FEV1) ≥ 80% (hazard ratio [HR], 3.10; 95% confidence interval [CI], 1.79-5.39; P < 0.001), and maintenance of immunotherapy for more than 3 years (HR, 1.82; 95% CI, 1.21-2.72; P = 0.004) were significant predictors of asthma remission during SCIT. In 284 patients on SCIT with HDM alone, initial specific immunoglobulin E (IgE) levels to Dermatophagoides pteronyssinus and Dermatophagoides farinae did not show significant difference between remission and non-remission group after adjusting demographic variables. In conclusion, SCIT was effective and safe treatment modality for patients with AA. Initial FEV1 ≥ 80% and immunotherapy more than 3 years were found to be associated with favorable clinical responses to SCIT.

Emerging Hop Japanese Pollinosis in Asia.

Hop Japanese (Hop J) pollen has been considered one of the major causative pollen allergens in Far East Asia in the autumn season. The sensitization rate, pollen count, and allergenicity of Hop J pollens are increasing in this region because of increased air pollution and global warming. However, commercial skin test agents for the diagnosis and allergen extracts for the allergen immunotherapy are not available. This review summarizes recent data on clinical impact of Hop J pollinosis in order to facilitate the development of diagnostic and therapeutic agents for this region.

Etiologies of altered level of consciousness in the emergency room.

Altered levels of consciousness (ALCs) is a challenging issue; however, data describing its etiology and frequency are lacking. This study aimed to clarify and classify the etiologies of ALCs in the emergency room (ER) and to evaluate their destinations and the form of discharge. This retrospective study included patients with an ALC who visited the ER of a university hospital between January 2018 and December 2020. The cause and classification of the ALCs were carefully determined by a consortium of board-certified faculty members in emergency medicine, internal medicine, and neurology. The reference point for determining the etiology of ALC was discharge from the ER. In total, 2028 patients with ALCs were investigated. More than half (1037, 51.1%) visited the ER between 9:00 and 18:00. The most common etiology was systemic infection (581, 28.6%), followed by metabolic causes (455, 22.4%), and stroke (271, 13.4%). The two leading etiologies were extracranial and had a majority of the cases (1036, 51.5%). The overall mortality rate was 17.2%. This study provides fundamental information on ALC in the ER. Although intracranial etiologies have been foregrounded, this study demonstrated that extracranial etiologies are the main cause of ALC in the ER.

Detection of circulating IgG autoantibody to FcεRIα in sera from chronic spontaneous urticaria patients.

BACKGROUNDS: Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by itchy wheals of at least 6 weeks in duration, wherein the autoimmune mechanism is involved to activate IgE receptors (FcεRIα) on mast cells. We aimed to assess levels of IgG autoantibody against FcεRIα in sera from CSU patients using dot-blot immunoassay. METHODS: We performed a hospital-based cross-sectional study of 125 CSU patients (64 ASST-positive, 61 ASST-negative) and 64 age-and sex-matched healthy controls. The cut-off value of IgG FcεRIα autoantibody was determined as the mean intensity plus two standard deviations of values in controls. Positivity for IgG autoantibody to FcεRIα was analyzed according to clinical parameters of disease duration, urticaria activity score (UAS), ASST, response to antihistamine treatment, complement levels, and the presence of other autoantibodies. Nonparametric tests were applied for statistical analyses. RESULTS: IgG positivity to FcεRIα was noted in 24.8% of CSU patients and was significantly more frequent in ASST-positive patients than in ASST-negative patients (32.8% vs 16.4%, P = 0.040). Only 3.1% of healthy controls had this autoantibody. Complement 3 levels were significantly lower in anti-FcεRIα antibody-positive patients than antibody-negative patients (109.8 ± 19.9 vs 123.1 ± 30.9, P = 0.035). No significant associations were found between IgG positivity to FcεRIα and UAS, serum total IgE levels, atopic status, clinical responses to antihistamines, or the presence of anti-thyroid and anti-nuclear antibodies. CONCLUSION: These findings suggest that circulating IgG autoantibody to FcεRIα in a subset of patients may be involved in the autoimmune mechanism of CSU. Further studies are needed to clarify its clinical significance.

The HLA-B*13:01 and the dapsone hypersensitivity syndrome in Korean and Asian populations: genotype- and meta-analyses.

BACKGROUND: The human leukocyte antigen (HLA)-B*13:01 was reported as an important risk factor for dapsone hypersensitivity syndrome (DHS) in Chinese and Thai populations. RESEARCH DESIGN AND METHODS: From the Korean nationwide registry, seven subjects with previous DHS were included. Their HLA allele/phenotype frequencies were compared with 8 dapsone-tolerant subjects recruited from a single institution, and general population (n = 485) in Korea. The authors also performed a meta-analysis with these data using previous Chinese and Thai studies. RESULTS: Among the seven DHS subjects, 85.7% presented with the HLA-B*13:01 allele. The HLA-C*03:04, HLA-DRB1*12:02 (both in linkage disequilibrium with HLA-B*13:01), and HLA-A*02:01 alleles were also presented in 85.7%, 71.4%, and 71.4%, respectively. Subjects with HLA-B*13:01 were susceptible to developing DHS compared to dapsone-tolerant controls (odds ratio [OR]: 73.667) and the Korean general population (OR: 139.500). HLA-C*03:04 (OR: 40.935), HLA-DRB*12:02 (OR: 36.613), and HLA-A*02:01 (OR: 5.862) showed similar results. In meta-analysis, HLA-B*13:01 was associated with dapsone-induced hypersensitivity (overall OR: 42.692), and subgroup analyses according to the control types demonstrated similar results (OR:43.694 and 41.866, respectively). CONCLUSIONS: Similar to previous Asian population studies, HLA-B*13:01 is significantly associated with the risk of DHS in Korea. These associations may be useful for preventing DHS and improving drug safety.

Serum Levels of Eosinophil-Derived Neurotoxin: A Biomarker for Asthma Severity in Adult Asthmatics.

PURPOSE: Eosinophilic inflammation is a key component of severe asthma (SA). However, there has been no reliable serum biomarker for the eosinophilic inflammation of SA. We hypothesized that serum eosinophil-derived neurotoxin (EDN) could predict the eosinophilic inflammation of SA in adult asthmatics. METHODS: Severe asthmatics (n = 235), nonsevere asthmatics (n = 898), and healthy controls (n = 125) were enrolled from Ajou University Hospital, South Korea. The serum levels of EDN and periostin were measured by enzyme-linked immunosorbent assay and compared between severe and nonsevere asthmatics. Their associations with total eosinophil count (TEC) and clinical parameters were evaluated; clinical validation of the K-EDN kit for the measurement of serum EDN was evaluated. RESULTS: Severe asthmatics were older and had longer disease duration with significantly lower levels of forced expiratory volume in 1 second and methacholine PC20 than nonsevere asthmatics. Significant differences were found in TEC or sputum eosinophil count (%) between the groups. The serum levels of EDN and periostin were significantly higher in severe asthmatics than in nonsevere asthmatics and in healthy controls (all P < 0.05). Although significant correlations were found between serum EDN levels measured by the 2 kits (ρ = 0.545, P < 0.0001), higher correlation coefficients between serum EDN levels measured by the K-EDN kit and TEC were higher (ρ = 0.358, P < 0.0001) than those between serum EDN levels measured by the MBL kit and TEC (ρ = 0.319, P < 0.0001) or serum periostin level (ρ = 0.222, P < 0.0001). Multivariate regression analysis demonstrated that serum EDN levels measured by the K-EDN kit predicted the phenotype of SA (P = 0.003), while 2 other biomarkers did not. CONCLUSIONS: The serum EDN level may be a useful biomarker for assessing asthma severity in adult asthmatics.

An update on the management of aspirin-exacerbated respiratory disease.

INTRODUCTION: Clinical features of aspirin-exacerbated respiratory disease (AERD) consist of moderate to severe asthma associated with chronic rhinosinusitis (CRS), which are derived from overproduction of cysteinyl leukotrienes along with chronic type 2 mediated inflammation in the upper and lower airway mucosa. Area covered: This review provides recent up-to-date information regarding phenotypes of AERD and encompasses comprehensive diagnostic methods and treatment options. To confirm the diagnosis of AERD, provocation testing via nasal, inhalation or the oral route of aspirin remains the gold standard; in vitro diagnostic methods are still not available. Essential management is to avoid cross-reacting cyclooxygenase 1 (COX-1) inhibitors along with use of highly selective COX-2 inhibitors and to maintain pharmacologic treatment depending on the severity of asthma and chronic rhinosinusitis. Recent biologics, including anti-IgE and anti-IL5 antibodies, are required in severe AERD patients with CRS. Aspirin desensitization can be recommended when indicated. Expert commentary: AERD is a heterogeneous disease in terms of severity and associated allergic disease. When performing diagnosis and treatment for AERD, such disease characteristics need to be kept in mind.

Prevalence and clinical characteristics of local allergic rhinitis to house dust mites.

PURPOSE OF REVIEW: Local allergic rhinitis (LAR) is a recently classified subtype of rhinitis defined by a nasal allergic response in patients without systemic evidence of atopy. Recent studies have reported the prevalence, clinical course, culprit allergens, diagnostic methods and treatment outcomes of LAR. The purpose of this review is to summarize the most relevant and updated scientific evidence for LAR, especially focusing on its prevalence and clinical characteristics. RECENT FINDINGS: LAR is found in a significant proportion (3.7-61.9%) of patients previously diagnosed with nonallergic rhinitis, but the prevalence may differ among ethnic groups and countries. Common allergens of LAR are similar to those of allergic rhinitis, in which house dust mites are the most common cause, followed by grass pollen, tree pollen, weed pollen and animal dander confirmed by provocation tests. Although the nasal provocation test to a single allergen is considered the gold standard method, the detection of allergen-specific IgE and other inflammatory mediators from nasal secretions and the basophil activation test can assist in the diagnosis of LAR. Conjunctivitis and asthma are the most common comorbid conditions, and the occurrence rate of asthma increases over period. However, the conversion rate to allergic rhinitis was not significantly different between LAR and healthy controls. SUMMARY: LAR is a well-differentiated entity of rhinitis, which should be considered in patients with persistent and severe symptoms without any systemic evidence of atopy. Further research is needed to investigate the long-term outcome, and geographic and ethnic differences of LAR.

A Retrospective Study of Clinical Response Predictors in Subcutaneous Allergen Immunotherapy With House Dust Mites for Allergic Rhinitis.

PURPOSE: House dust mites (HDM) are major allergens that cause allergic rhinitis (AR). Allergen-specific subcutaneous immunotherapy (SCIT) has been shown to be clinically beneficial in many clinical trials. Such trials, however, are not reflective of all patient populations. The aim of this study was to describe the efficacy and safety of SCIT in routine clinical practice in Korean adults with AR sensitized to HDM. METHODS: We reviewed medical records of 304 patients with AR treated at an allergy clinic of a tertiary hospital using SCIT with aluminum hydroxide-adsorbed allergen extract targeting HDM alone or with pollens for at least 1 year from 2000 to 2012. Patients with asthma were excluded. Rates of remission, defined as no further requirement of maintenance medication, over time were determined by means of life tables and extension of survival analysis. Specific immunoglobulin E (IgE) levels to HDM were categorized into 6 classes. RESULTS: The mean time until achieving remission was 4.9±0.1 years, and the cumulative incidence of remission from AR was 76.6%. Severe AR (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.23-0.69; P=0.001), specific IgE levels to HDM ≥17.5 kU/L (OR, 1.85; 95% CI, 1.01-3.37; P=0.045), and duration of immunotherapy ≥3 years (OR, 7.37; 95% CI, 3.50-15.51; P<0.001) were identified as significant predictors of clinical remission during SCIT for patients with AR sensitized to HDM. Overall, 73 patients (24.0%) experienced adverse reactions to SCIT, and only 1 case of anaphylaxis (0.3%) developed. CONCLUSIONS: SCIT with HDM was found to be effective and safe for patients with AR. Specific IgE levels to HDM and a duration of SCIT ≥3 years may be predictors of clinical responses to SCIT in AR patients.

Therapeutic Effect of Omalizumab in Severe Asthma: A Real-World Study in Korea.

PURPOSE: Omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, has proved to be effective for the treatment of severe asthma. However, there is no direct evidence of effectiveness of omalizumab in Korean patients with severe asthma. We sought to evaluate the real-world effectiveness of omalizumab in Korean adult patients suffering from severe asthma and to identify predictors of favorable response. METHODS: A retrospective analysis of electrical medical records was performed on severe allergic asthmatic patients with omalizumab treatment group (OT group) for more than 6 months between March 2008 and February 2016. Propensity score matching was applied to define the standardized treatment control group (STC group) treated without omalizumab. Asthma-related outcomes were compared between the 2 groups, and analyzed before and after omalizumab use in the OT group. Responders to treatment were defined as patients showing >50% reduction in asthma exacerbations and/or systemic steroid requirement during the outcome period. RESULTS: One hundred twenty-four patients with severe asthma (62 in the OT group; 62 in the STC group) were enrolled in the study. Proportion of patients having the reduction of asthma exacerbation (53.2% vs 35.5%, P=0.015) and the rate of responders (67.7% vs 41.9%, P=0.007) were significantly higher in the OT group than in the STC group. Significant reductions were noted in asthma exacerbation (P=0.006), hospitalization (P=0.009), hospitalization days (P=0.006), systemic corticosteroid requirements (P=0.027), and sputum eosinophil count (P=0.031) in OT group compared with STC group. There were no significant differences in changes of forced expiratory volume in the 1 second (FEV1) levels between the 2 groups. No predictors of responders were found for omalizumab treatment. CONCLUSIONS: Omalizumab can reduce exacerbations/hospitalization/systemic steroid burst in Korean adult patients with severe asthma.

Prevalence and Clinical Characteristics of Local Allergic Rhinitis to House Dust Mites.

Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy. The aim of this study was to evaluate the prevalence and clinical characteristics of LAR in Korean rhinitis patients compared to allergic rhinitis (AR) and non-allergic rhinitis (NAR). A total of 304 rhinitis patients were enrolled from November 2014 to March 2016. A skin prick test, serum total and specific immunoglobulin E, and a nasal provocation test (NPT) with house dust mite (HDM) were performed on all patients. Subjects also documented changes in rhinitis symptoms before and after NPT. Seventy-four patients with nasal hyper-reactivity and 80 patients with subclinical allergy were excluded. AR was diagnosed in 69 (46.0%) patients, NAR in 75 (50.0%) patients, and LAR to HDM in 6 (4.0%) patients. The average medication score and disease duration of each group were 14.5 points and 77.6 months in AR, 12.1 point and 51.1 months in NAR, and 17.7 point and 106.0 months in LAR, respectively. There were no significant differences in the baseline nasal symptom score of the three groups. However, after NPT with HDM, the score of rhinitis, itching, and obstructive were 4.83±1.47 vs. 1.95±2.53, 3.00±2.10 vs. 1.45±2.06, and 5.50±1.38 vs. 2.57±2.84 in LAR and NAR, respectively (p<0.05). LAR patients had longer duration of disease and tended to be older and have higher medication score than other rhinitis patients.

Sleep quality in rheumatoid arthritis, and its association with disease activity in a Korean population.

BACKGROUND/AIMS: The aim of this study was to compare the sleep quality between rheumatoid arthritis (RA) patients and healthy controls; and to evaluate the relationship between RA disease activity and sleep quality in Korea. METHODS: A total of 130 RA patients and 67 age- and sex-matched healthy controls were enrolled in a comparative study of sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Age, gender, concomitant medication, erythrocyte sedimentation rate, serum C-reactive protein, Beck Depression Inventory second edition (BDI-II), 28 joints disease activity score (DAS28), pain visual analog scale (VAS), and PSQI were analyzed as covariates. We also analyzed the sleep quality of RA patients according to the disease activity (DAS28 ≤ 3.2, 3.2 < DAS28 < 5.1, and DAS28 ≥ 5.1, respectively). RESULTS: The total PSQI score and the frequency of poor sleep quality, were higher in the RA patients (5.62 ± 4.19, 38.5%) than in the control subjects (3.57 ± 2.17, 13.4%). The patients with poor sleep quality (PSQI > 5) were older and had a higher BDI-II and VAS score than the patients without sleep disturbance (PSQI ≤ 5). The score in subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, daytime dysfunction, total PSQI, and frequency of poor sleep quality were increased when RA activity was high. CONCLUSIONS: Sleep disturbance was observed in RA patients (38.5%), and high RA disease activity was associated with poor sleep quality in Korea.