Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study.

PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.

Clinical outcomes of mild to moderate coronavirus disease 2019 patients treated with Regdanvimab in delta-variant outbreak: Retrospective cohort study.

Regdanvimab is a novel neutralizing antibody agent used for the treatment of coronavirus disease 2019 (COVID-19). However, the effectiveness of regdanvimab in delta-variant patients has rarely been investigated. We examined the clinical outcomes and adverse events in COVID 19 patients treated with regdanvimab in the delta-variant era. Data were collected from laboratory-confirmed COVID-19 hospitalized patients who received regdanvimab in 2021 and categorized into pre-delta and delta variant groups. The primary outcome was the need for oxygen therapy. Rescue therapy, clinical improvement, and adverse events were analyzed. Among 101 patients treated with regdanvimab, 31 (30.7%) were delta patients and 49 (48.5) were pre-delta patients. 64.4% were male, the mean age was 60.3 years, and 70 patients (69%) had at least one underlying disease. The median interval from symptom onset to injection was 4 days. Twenty-three patients (23%) needed oxygen therapy, including 9 (29%) in the delta and 8 (16.3%) in the pre-delta group. (P = .176) The risk of early oxygen supplement was higher in the delta group (adjusted hazard ratio (aHR), 6.75; 95% confidence interval(CI), 1.53-29.8). The in-hospital survival rate was 100%, and no patients were admitted to the intensive care unit. Adverse events occurred in 43% of patients:13 (42%) delta patients and 23 (47%) pre-delta patients had any adverse events (P = .661). Patients treated with regdanvimab 4 days after symptom onset showed a favorable prognosis (aHR, 0.26; 95% CI, 0.26-0.91). We found that the high-risk mild to moderate COVID-19 patients treated with regdanvimab showed similar disease progression in delta-variant patients and pre-delta variants; however, we need to be more closely observed delta-variant patients than those in the pre-delta group despite regdanvimab treatment due to rapid disease aggravation.

Baseline Cohort Profile of the Korean Chronic Cough Registry: A Multicenter, Prospective, Observational Study.

PURPOSE: The Korean Chronic Cough Registry study was initiated to characterize patients with chronic cough (CC) and investigate their outcomes in real-world clinical practice. This report aims to describe the baseline cohort profile and study protocols. METHODS: This multicenter, prospective observational cohort study included newly referred CC patients and those already being treated for refractory or unexplained chronic cough (RUCC). Cough status was assessed using a visual analog scale, the Leicester Cough Questionnaire (LCQ), and the Cough Hypersensitivity Questionnaire (CHQ). RESULTS: A total of 610 patients (66.9% women; median age 59.0 years) were recruited from 18 centers, with 176 being RUCC patients (28.9%). The median age at CC onset was 50.1 years, and 94.4% had adult-onset CC (≥ 19 years). The median cough duration was 4 years. Compared to newly referred CC patients, RUCC patients had a longer cough duration (6.0 years vs. 3.0 years) but had fewer symptoms and signs suggesting asthma, rhinosinusitis, or gastroesophageal acid reflux disease. Subjects with RUCC had lower LCQ scores (10.3 ± 3.3 vs. 11.6 ± 3.6; P < 0.001) and higher CHQ scores (9.1 ± 3.9 vs. 8.4 ± 4.1; P = 0.024). There were no marked differences in the characteristics of cough between refractory chronic cough and unexplained chronic cough. CONCLUSIONS: Chronic cough typically develops in adulthood, lasting for years. Cough severity and quality of life impairment indicate the presence of unmet clinical needs and insufficient cough control in real-world clinical practice. Longitudinal follow-up is warranted to investigate the natural history and treatment outcomes.

Clinical Relevance of Staphylococcus aureus Nasal Colonization and Staphylococcal Enterotoxin-Specific IgE Sensitization in Late-Onset Asthma.

This prospective observational study examined whether Staphylococcus aureus (SA) nasal colonization and staphylococcal enterotoxin (SE)-specific IgE sensitization synergistically affect clinical outcomes of adults with late-onset asthma (onset age ≥ 40 years). Nasal swabs were taken to evaluate SA colonization. Serum SE-IgE level was measured. Subjects were classified into 4 groups according to SA colonization and SE-IgE sensitization positivity. Among 181 patients with late-onset asthma recruited, the proportions of SA/SE (‒/‒), SA/SE (+ /‒), SA/SE (‒/ +), and SA/SE (+ / +) were 33.7%, 15.5%, 28.2%, and 22.6%, respectively. Severe asthma was more frequent in the SA/SE (+ / +) group than in the SA/SE (‒/‒) group (41.5% vs. 13.1%). The relationship of SA/SE (+ / +) with severe asthma was significant in multivariate logistic regression (vs. SA/SE (‒/‒); adjusted odds ratio: 4.36; 95% confidence intervals: 1.50‒12.73; p = 0.007), whereas SA/SE (+ /‒) or SA/SE (‒/ +) was not. In conclusion, SA nasal colonization and SE-IgE sensitization may synergistically affect disease severity in late-onset asthmatics.

Staphylococcal Enterotoxin-Specific IgE Sensitization: A Potential Predictor of Fixed Airflow Obstruction in Elderly Asthma.

PURPOSE: Staphylococcus aureus enterotoxin-specific immunoglobulin E (SE-sIgE) sensitization tends to increase with age and is known to be associated with asthma and severity in older adults. However, the long-term impact of SE-sIgE in the elderly remains unknown. This study aimed to examine the relationships between SE-sIgE and fixed airflow obstruction (FAO) in a cohort of elderly asthmatics. METHODS: A total of 223 elderly asthmatics and 89 controls were analyzed. Patients were assessed for demographics, history of chronic rhinosinusitis (CRS), asthma duration, acute exacerbation frequency, and lung function at baseline and then were prospectively followed up for 2 years. Serum total IgE and SE-sIgE levels were measured at baseline. Airflow obstruction was defined as forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio < 0.7 at baseline and FAO was defined as FEV1/FVC ratio < 0.7 over the 2-year follow-up. RESULTS: At baseline, the prevalence of airflow obstruction was 29.1%. Patients with airflow obstruction were significantly more likely to be male, and have a positive smoking history, comorbid CRS, and higher levels of SE-sIgE than those without airflow obstruction. Multivariate logistic regression analysis showed that airflow obstruction was significantly associated with current smoking and SE-sIgE sensitization at baseline. After the 2-year follow-up, baseline SE-sIgE sensitization was consistently related to FAO. Meanwhile, the number of exacerbations per year was significantly correlated with SE-sIgE levels. CONCLUSIONS: Baseline SE-sIgE sensitization was significantly associated with the number of asthma exacerbations and FAO after the 2-year follow-up in elderly asthmatics. These findings warrant further investigation of the direct and mediating roles of SE-sIgE sensitization on airway remodeling.

Health-Related Quality of Life and Its Determinants in Chronic Cough: The Korean Chronic Cough Registry Study.

PURPOSE: Chronic cough (CC) is associated with health-related quality of life (HRQoL) impairment. However, the determinants of HRQoL are under-investigated. METHODS: Patients aged 19-80 years with CC were prospectively recruited from 10 referral clinics. Comparisons were made with age- and sex-matched controls (1:4 ratio) selected from a Korean general population survey database; 1) a group without current cough (non-cough controls) and 2) another group without major chronic illnesses (healthy controls). HRQoL was assessed using the EuroQoL 5-dimension (EQ-5D) index. In CC patients, cough-specific patient-reported outcomes (PROs) were additionally measured. Cross-sectional analyses were performed to evaluate demographic and clinical parameters associated with the EQ-5D index of CC patients. RESULTS: A total of 200 CC patients (137 newly referred with CC and 63 refractory or unexplained CC [RUCC] patients), 800 non-cough controls, and 799 healthy controls were analyzed. The EQ-5D index of CC patients was significantly lower than that of non-cough controls or healthy controls (0.82 ± 0.14 vs 0.92 ± 0.14/0.96 ± 0.08; P < 0.001, respectively). The index was also associated with older age (≥ 60 years), female sex, and comorbidities such as asthma or depression. Among the patients with CC, the index was significantly lower in patients with RUCC than in those with newly referred CC, being treated with codeine or cough neuromodulators, or with cough-related fatigue. In Spearman analyses, the EQ-5D index correlated with cough-specific quality of life and cough severity scores, not with throat sensation or cough trigger scores. CONCLUSIONS: The HRQoL impairment of CC patients was associated with older age, female sex, and comorbidities but it was also affected by cough severity, complications, treatments, and treatment responses. Longitudinal studies are warranted to further understand and improve the HRQoL of CC patients.

Relationship between asthma and sarcopenia in the elderly: a nationwide study from the KNHANES.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cough Presentation and Cough-Related Healthcare Utilization in Tertiary Care: Analysis of Routinely Collected Academic Institutional Database.

PURPOSE: Routinely collected data (RCD) from electronic health records (EHR) are useful for studying disease epidemiology in the real world. We examined cough presentation and cough-related healthcare utilization using an academic institutional EHR database in Korea. METHODS: In this retrospective cohort study, patients with subacute (3-8 weeks) or chronic cough (> 8 weeks in duration) referred to allergy and asthma clinics were studied. Cases were identified using the search term "cough" or "coughing," which is the chief complaint, in the data fields. Structured data, including demographics, medical history, symptoms, and diagnostic tests, were analyzed. Healthcare utilization was assessed for drug prescriptions, additional tests, or outpatient visits for 1 year. RESULTS: Cough was the chief complaint in 13,223 cases (46.7%) among 28,312 new referrals for 8 years. A total of 3810 subacute and 7150 chronic cough patients were analyzed. The common demographic profile was middle-aged woman (mean age 52.1 years), reported in 63% of the cases. Cough was frequently accompanied by anterior nasal (about 50%), lower airway (30%), or acid reflux disease symptoms (20%), and by test abnormalities in chest X-rays (14%), spirometry (23%), or T2 inflammation markers (40%). Chronic cough patients frequently required additional tests (chest CT scan: 24%), drug prescriptions (codeine: 21.5% and oral steroids: 9.9%), and long-term healthcare utilization (16.0%) for 1 year. CONCLUSIONS: Cough is a common chief complaint at allergy and asthma clinics, but the clinical presentation may be heterogeneous. Further studies are needed to understand long-term outcomes and reduce the disease burden.

Clusters of Severe Eosinophilic Asthma in a Korean Asthma Cohort.

BACKGROUND: 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. OBJECTIVES: We aimed to describe the characteristics of SEA and identify its patient subgroups. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Efficacy of non-sedating H1-receptor antihistamines in adults and adolescents with chronic cough: A systematic review.

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.

Prevalence and diagnostic values of laboratory animal allergy among research personnel.

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.

Oleoylethanolamide induces eosinophilic airway inflammation in bronchial asthma.

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.

Impact and disease burden of chronic cough.

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.

Patients' experiences of asthma exacerbation and management: a qualitative study of severe asthma.

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.

Specialist Perception of Severe Asthma in Korea: A Questionnaire Survey.

The Working Group on Severe Asthma of the Korean Academy of Allergy and Clinical Immunology recently published an expert opinion paper on the management of severe asthma in Korea. When developing a consensus, the working group encountered several diagnostic and treatment issues and decided to perform a questionnaire survey of Korean specialists with regard to severe asthma. An e-mail with a uniform resource locator link to the questionnaire was sent to 121 asthma specialists, of whom 44.6% responded. The most commonly accepted definitions of severe asthma were a history of fatal exacerbation or an asthma-triggered need for mechanical ventilation, 3-4 oral corticosteroid (OCS) bursts/year, and maintenance of OCS therapy for 3-6 months per year. Before diagnosing severe asthma, most physicians contemplate chest computed tomography, seek to control chronic rhinosinusitis, and consider poor inhaler compliance. For patients with uncontrolled severe asthma accompanied by type 2 (T2)-high inflammation, most biologics available in Korea were considered appropriate, but gaps were apparent in terms of T2-low asthma treatments. These findings about specialist perception of diagnosis and treatment of severe asthma will inform the use of emerging new drugs and facilitate personalized therapy.

Comparing Inhaler Use Technique Based on Inhaler Type in Elderly Patients with Respiratory Disease.

BACKGROUND: The aim of this study was to investigate inhaler device handling in elderly patients. Inhaler devices with respect to misuse and error correction were also compared. METHODS: Inhaler use technique was assessed using standardized checklists at the first visit and 3-month follow-up visit after retraining. The primary outcome was difference in the acceptable use ratio among inhaler devices. Secondary outcomes included differences in error correction, the most common step of misuse, and factors affecting the accuracy of inhaler use. RESULTS: A total of 251 patients (mean age, 76.4 years) were included. The handling of 320 devices was assessed in the study. All patients had been trained before. However, only 24.7% of them used inhalers correctly. Proportions of acceptable use for Evohaler, Respimat, Turbuhaler, Ellipta, and Breezhaler/Handihaler were 38.7%, 50.0%, 61.4%, 60.8%, and 43.2%, respectively (p=0.026). At the second visit, the acceptable use ratio had increased. There were no significant differences among inhaler types (Evohaler, 63.9%; Respimat, 86.1%; Turbuhaler, 74.3%; Ellipta, 64.6%; and Breezhaler/Handihaler, 65.3% [p=0.129]). In multivariate analysis, body mass index, Turbuhaler, and Ellipta showed positive correlations with acceptable use of inhalers, whereas Chronic Obstructive Pulmonary Disease Assessment Test score showed a negative correlation. CONCLUSION: Although new inhalers have been developed, the accuracy of inhaler use remains low. Elderly patients showed more errors when using pressurized metered-dose inhalers than using dry powder inhalers and soft-mist inhalers. However, there were no significant differences in misuse among inhaler devices after individual training. Results of this study suggests that repeat training is more important than inhaler type.

The role of allergen-specific IgE in predicting allergic symptoms on dog and cat exposure among Korean pet exhibition participants.

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.

Metagenome analysis using serum extracellular vesicles identified distinct microbiota in asthmatics.

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.

Evaluation and Management of Difficult-to-Treat and Severe Asthma: An Expert Opinion From the Korean Academy of Asthma, Allergy and Clinical Immunology, the Working Group on Severe Asthma.

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.

Impact of Chronic Cough on Health-Related Quality of Life in the Korean Adult General Population: The Korean National Health and Nutrition Examination Survey 2010-2016.

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.