Development of the Rapid Cough Questionnaire: Key item identification.

BACKGROUND: The Leicester Cough Questionnaire (LCQ) is a reliable tool for measuring the multidimensional impact of cough on patients' quality of life; however, its scoring algorithm is lengthy and complex for routine clinical use. OBJECTIVE: The study aimed to develop a simplified version of the LCQ, the Rapid Cough Questionnaire (RCQ), as a substitue in clinical practice and validate the RCQ using an independent cohort. METHODS: To select items for the RCQ score, a correlation network was used to determine the items from each domain that were strongly correlated with the total LCQ score. The final items for the RCQ were selected on the basis of the centrality of the node degree, betweenness, and closeness in the correlation network. RESULTS: The RCQ score was derived from 3 items: tiredness (LCQ3) in the physical domain, the feeling of being fed up (LCQ13) in the psychological domain, and annoyance with partner/family/friends (LCQ19) in the social domain. The correlation between the LCQ and RCQ was high, with a coefficient of 0.93 (P < .001). The mean score of the RCQ was 11.2 ± 3.2, with scores ranging from 5.15 to 19.55. The minimal clinically important difference in the RCQ score was calculated to be 1.6 using a distribution-based method. The concurrent validity of the LCQ and the RCQ with cough numeric rating scale was similar. In the validation cohort, the correlation between the LCQ and RCQ scores was consistent regardless of sex and etiology. CONCLUSION: The RCQ score, which is concise, reliable, and valid, can be a valuable tool for patient assessment, particularly in clinical practice.

Prospective direct comparison of biologic treatments for severe eosinophilic asthma: Findings from the PRISM study.

BACKGROUND: Although various monoclonal antibodies have been used as add-on therapy for severe eosinophilic asthma (SEA), to the best of our knowledge, no direct head-to-head comparative study has evaluated their efficacy. OBJECTIVE: To compare the efficacy of reslizumab, mepolizumab, and dupilumab in patients with SEA. METHODS: This was a multicenter, prospective observational study in patients with SEA who had received 1 of these biologic agents for at least 6 months. Cox proportional hazard models were used to compare the risk of the first exacerbation event, adjusting for sputum or blood eosinophils and common asthma-related covariates. The annual exacerbation rate was analyzed using a negative binomial model, and a mixed-effect model was used to analyze changes in forced expiratory volume in 1 second and asthma control test score over time. RESULTS: A total of 141 patients with SEA were included in the analysis; 71 (50%) received dupilumab; 40 (28%) received reslizumab, and 30 (21%) received mepolizumab. During the 12-month follow-up, 27.5%, 43.3%, and 38.0% of patients in the reslizumab, mepolizumab, and dupilumab groups, respectively, experienced at least 1 exacerbation. However, after adjusting for confounding factors, the dupilumab and mepolizumab groups showed similar outcomes in time-to-first exacerbation, exacerbation rate, forced expiratory volume in 1 second, and asthma control test score to those of the reslizumab group. CONCLUSION: In patients with SEA, treatment with reslizumab, mepolizumab, and dupilumab resulted in comparable clinical outcomes within a 12-month period. TRIAL REGISTRATION: The cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939).

Cough Response to High-Dose Inhaled Corticosteroids in Patients with Chronic Cough and Fractional Exhaled Nitric Oxide Levels ≥ 25 ppb: A Prospective Study.

This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25 ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4 years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.

Association of Cough Severity with Asthma Control and Quality of Life in Patients with Severe Asthma.

PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.

Predictors of Early and Late Lung Function Improvement in Severe Eosinophilic Asthma on Type2-Biologics in the PRISM Study.

BACKGROUND: The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. OBJECTIVE: We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. METHODS: 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6 months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6 months of treatment. RESULTS: More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1 month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1 month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1 month, 39% exhibited improvement at 6 months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6 months of treatment (OR and 95% CI 1.75 [1.09-2.98]). CONCLUSION: Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response.

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.

WITHDRAWN: Prospective direct comparison of biological treatments on severe eosinophilic asthma: Findings from the PRISM study.

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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.

Effectiveness and Safety of Codeine and Levodropropizine in Patients With Chronic Cough.

BACKGROUND: Recent progress in chronic cough management includes controlling cough triggers and hypersensitivity using antitussives. Therefore, we investigated the effects and safety outcomes of antitussives, codeine and levodropropizine, in patients with chronic cough. METHODS: We conducted an open-label, randomized comparative trial with newly referred patients with chronic cough. Patients were orally administered codeine (60 mg/day) and levodropropizine (180 mg/day) for 2 weeks. Cough severity, including the visual analog scale (VAS), Cough Symptom Score (CSS), Leicester Cough Questionnaire (LCQ), and safety for each treatment were assessed. The primary outcome was VAS score changes before and after 2 weeks of treatment. RESULTS: Among the 88 participants, 45 and 43 in the codeine and levodropropizine groups, respectively, were included in the analysis. Changes in the VAS score were higher in the codeine group than in the levodropropizine group (35.11 ± 20.74 vs. 19.77 ± 24.83, P = 0.002). Patients administered codeine also had improved CSS (2.96 ± 2.35 vs. 1.26 ± 1.89, P < 0.001) and LCQ (3.28 ± 3.36 vs. 1.61 ± 3.53, P = 0.025) than those administered levodropropizine. Treatment-related adverse events, including drowsiness, constipation, and headaches, were more frequent in the codeine group than in the levodropropizine group. However, no significant differences existed in the adverse events leading to discontinuation. CONCLUSION: Codeine is an effective and generally well-tolerated antitussive for chronic cough. However, it may induce side effects in some patients. Individual responses and adverse events should be carefully monitored when codeine is used to treat chronic cough.

Characteristics of Specialist-Diagnosed Asthma-COPD Overlap in Severe Asthma: Observations from the Korean Severe Asthma Registry (KoSAR).

BACKGROUND: While the clinical characteristics and outcomes of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) have been frequently compared with those of COPD or asthma, the prevalence and features of ACO in patients with severe asthma are unclear. OBJECTIVES: Evaluation of the prevalence and clinical features of ACO using the Korean severe asthma registry. METHODS: At the time of registration, ACO was determined in patients with severe asthma by attending specialists. Patients were classified into ACO and non-ACO groups, and the demographic and clinical characteristics of these two groups were compared. RESULTS: Of 482 patients with severe asthma, 23.7% had ACO. Patients in the ACO group were more likely to be male (P < .001), older (P < .001), and ex- or current smokers (P < .001) compared with those in the non-ACO group. Patients in the ACO group had lower mean forced expiratory volume in 1 second (P < .001) and blood eosinophil percentage (P = .006), but higher blood neutrophil percentage (P = .027) than those in the non-ACO group. The ACO group used more inhaled long-acting muscarinic antagonist (P < .001), methylxanthine (P = .001), or sustained systemic corticosteroid (P = .002). In addition, unscheduled emergency department visits due to exacerbation were more frequent in the ACO group (P = .006). CONCLUSION: Among patients with severe asthma, those with ACO were older, predominantly male, and were more likely to have a smoking history than those with asthma only. Patients with ACO used more systemic corticosteroid and had more frequent exacerbations related to emergency department visits than those with severe asthma only.

Chronic cough in the elderly.

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?

Impact of Cough and Unmet Needs in Chronic Cough: A Survey of Patients in Korea.

PURPOSE: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Diagnostic accuracy of fractional exhaled nitric oxide measurement in predicting cough-variant asthma and eosinophilic bronchitis in adults with chronic cough: A systematic review and meta-analysis.

BACKGROUND: Individual studies have suggested the utility of fractional exhaled nitric oxide (Feno) measurement in detecting cough-variant asthma (CVA) and eosinophilic bronchitis (EB) in patients with chronic cough. OBJECTIVE: We sought to obtain summary estimates of diagnostic test accuracy of Feno measurement in predicting CVA, EB, or both in adults with chronic cough. METHODS: Electronic databases were searched for studies published until January 2016, without language restriction. Cross-sectional studies that reported the diagnostic accuracy of Feno measurement for detecting CVA or EB were included. Risk of bias was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy of Feno measurement. RESULTS: A total of 15 studies involving 2187 adults with chronic cough were identified. Feno measurement had a moderate diagnostic accuracy in predicting CVA in patients with chronic cough, showing the summary area under the curve to be 0.87 (95% CI, 0.83-0.89). Specificity was higher and more consistent than sensitivity (0.85 [95% CI, 0.81-0.88] and 0.72 [95% CI, 0.61-0.81], respectively). However, in the nonasthmatic population with chronic cough, the diagnostic accuracy to predict EB was found to be relatively lower (summary area under the curve, 0.81 [95% CI, 0.77-0.84]), and specificity was inconsistent. CONCLUSIONS: The present meta-analyses indicated the diagnostic potential of Feno measurement as a rule-in test for detecting CVA in adult patients with chronic cough. However, Feno measurement may not be useful to predict EB in nonasthmatic subjects with chronic cough. These findings warrant further studies to validate the roles of Feno measurement in clinical practice of patients with chronic cough.

Eco-friendly porous concrete using bottom ash aggregate for marine ranch application.

This article presents the test results of an investigation carried out on the reuse of coal bottom ash aggregate as a substitute material for coarse aggregate in porous concrete production for marine ranch applications. The experimental parameters were the rate of bottom ash aggregate substitution (30%, 50% and 100%) and the target void ratio (15%, 20% and 25%). The cement-coated granular fertiliser was substituted into a bottom ash aggregate concrete mixture to improve marine ranch applications. The results of leaching tests revealed that the bottom ash aggregate has only a negligible amount of the ten deleterious substances specified in the Ministry of Environment - Enforcement Regulation of the Waste Management Act of Republic Korea. The large amount of bubbles/air gaps in the bottom ash aggregate increased the voids of the concrete mixtures in all target void ratios, and decreased the compressive strength of the porous concrete mixture; however, the mixture substituted with 30% and 10% of bottom ash aggregate and granular fertiliser, respectively, showed an equal strength to the control mixture. The sea water resistibility of the bottom ash aggregate substituted mixture was relatively equal to that of the control mixture, and also showed a great deal of improvement in the degree of marine organism adhesion compared with the control mixture. No fatality of fish was observed in the fish toxicity test, which suggested that bottom ash aggregate was a harmless material and that the combination of bottom ash aggregate and granular fertiliser with substitution rates of 30% and 10%, respectively, can be effectively used in porous concrete production for marine ranch application.

Classification and implementation of asthma phenotypes in elderly patients.

BACKGROUND: No attempt has yet been made to classify asthma phenotypes in the elderly population. It is essential to clearly identify clinical phenotypes to achieve optimal treatment of elderly patients with asthma. OBJECTIVES: To classify elderly patients with asthma by cluster analysis and developed a way to use the resulting cluster in practice. METHODS: We applied k-means cluster to 872 elderly patients with asthma (aged ≥ 65 years) in a prospective, observational, and multicentered cohort. Acute asthma exacerbation data collected during the prospective follow-up of 2 years was used to evaluate clinical trajectories of these clusters. Subsequently, a decision-tree algorithm was developed to facilitate implementation of these classifications. RESULTS: Four clusters of elderly patients with asthma were identified: (1) long symptom duration and marked airway obstruction, (2) female dominance and normal lung function, (3) smoking male dominance and reduced lung function, and (4) high body mass index and borderline lung function. Cluster grouping was strongly predictive of time to first acute asthma exacerbation (log-rank P = .01). The developed decision-tree algorithm included 2 variables (percentage of predicted forced expiratory volume in 1 second and smoking pack-years), and its efficiency in proper classification was confirmed in the secondary cohort of elderly patients with asthma. CONCLUSIONS: We defined 4 elderly asthma phenotypic clusters with distinct probabilities of future acute exacerbation of asthma. Our simplified decision-tree algorithm can be easily administered in practice to better understand elderly asthma and to identify an exacerbation-prone subgroup of elderly patients with asthma.

Diagnostic properties of the methacholine and mannitol bronchial challenge tests: a comparison study.

BACKGROUND AND OBJECTIVE: Airway hyperresponsiveness is a common feature of asthma. Methacholine and mannitol are two representative agonists for bronchial challenge. They have theoretically different mechanisms of action, and may have different diagnostic properties. However, their difference has not been directly evaluated among Korean adults. In this study, we compare the diagnostic properties of methacholine and mannitol bronchial provocation tests. METHODS: Asthmatic patients and non-asthmatic controls were recruited prospectively from four referral hospitals in Korea. Participants were challenged with each of methacholine and mannitol inhalation on different days. Their diagnostic utility was evaluated by calculating their sensitivity and specificity for asthma diagnosis. Response-dose ratio was also compared. RESULTS: A total of 50 asthmatic adults and 54 controls were enrolled (mean age 43.8 years). The sensitivity and specificity of mannitol challenge (defined by a PD15 of <635 mg) were 48.0% and 92.6%, respectively, whereas those of methacholine (defined by a PC20 of <16 mg/mL) were 42.0% and 98.1%, respectively. Twenty asthmatic participants (24%) showed positive response to a single agonist only. In the receiver operating curve analyses using response-dose ratio values, area under the curve was 0.77 (95% confidence interval (CI): 0.68-0.86) for mannitol, and 0.89 (95% CI: 0.83-0.95) for methacholine. The correlations between log- transformed mannitol and methacholine response-dose ratios were significant but moderate (r = 0.683, P < 0.001). CONCLUSIONS: The present study demonstrated overall similar diagnostic properties of two diagnostic tests, but also suggested their intercomplementary roles for asthma. The clinical trial registration number at ClinicalTrial.gov is NCT02104284.

Strength and durability performance of alkali-activated rice husk ash geopolymer mortar.

This paper describes the experimental investigation carried out to develop the geopolymer concrete based on alkali-activated rice husk ash (RHA) by sodium hydroxide with sodium silicate. Effect on method of curing and concentration of NaOH on compressive strength as well as the optimum mix proportion of geopolymer mortar was investigated. It is possible to achieve compressive strengths of 31 N/mm(2) and 45 N/mm(2), respectively for the 10 M alkali-activated geopolymer mortar after 7 and 28 days of casting when cured for 24 hours at 60°C. Results indicated that the increase in curing period and concentration of alkali activator increased the compressive strength. Durability studies were carried out in acid and sulfate media such as H2SO4, HCl, Na2SO4, and MgSO4 environments and found that geopolymer concrete showed very less weight loss when compared to steam-cured mortar specimens. In addition, fluorescent optical microscopy and X-ray diffraction (XRD) studies have shown the formation of new peaks and enhanced the polymerization reaction which is responsible for strength development and hence RHA has great potential as a substitute for ordinary Portland cement concrete.

Novel Artificial Intelligence-Based Technology to Diagnose Asthma Using Methacholine Challenge Tests.

PURPOSE: The methacholine challenge test (MCT) has high sensitivity but relatively low specificity for asthma diagnosis. This study aimed to develop and validate machine learning (ML) models to improve the diagnostic performance of MCT for asthma. METHODS: Data from 1,501 patients with asthma symptoms who underwent MCT between 2015 and 2020 were analyzed. The patients were grouped as either the training (80%, n = 1,265) and test sets (20%, n = 236) depending on the time of referral. The conventional model (provocative concentration that causes a 20% decrease in forced expiratory volume in one second [FEV1]; PC20 ≤ 16 mg/mL) was compared with the prediction models derived from five ML methods: logistic regression, support vector machine, random forest, extreme gradient boosting, and artificial neural network. The area under the receiver operator characteristic curves (AUROC) and area under the precision-recall curves (AUPRC) of each model were compared. The prediction models were further analyzed using different input combinations of FEV1, forced vital capacity (FVC), and forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%) values obtained during MCT. RESULTS: In total, 545 patients (36.3%) were diagnosed with asthma. The AUROC of the conventional model was 0.856 (95% confidence interval [CI], 0.852-0.861), and the AUPRC was 0.759 (95% CI, 0.751-0.766). All the five ML prediction models had higher AUROC and AUPRC values than those of the conventional model, and random forest showed both highest AUROC (0.950; 95% CI, 0.948-0.952) and AUROC (0.909; 95% CI, 0.905-0.914) when FEV1, FVC, and FEF25%-75% were included as inputs. CONCLUSIONS: Artificial intelligence-based models showed excellent performance in asthma prediction compared to using PC20 ≤ 16 mg/mL. The novel technology could be used to enhance the clinical diagnosis of asthma.

Sex-related disparities in cough-associated symptoms across different age groups.

BACKGROUND: Sex-related disparities in the prevalence of chronic cough have been consistently reported globally, with varying male-to-female ratios. OBJECTIVES: This study aimed to evaluate sex-related differences by comparing correlations between cough-related symptoms in males and females of different age groups. DESIGN: Adult patients with chronic cough who completed the Leicester Cough Questionnaire (LCQ) were recruited from 16 respiratory centers. METHODS: Correlation networks were constructed based on Spearman's correlation coefficients in males and females of various age groups. The distinct relationships of cough-related symptoms between subgroups were validated by an independent cohort. RESULTS: A total of 255 patients were enrolled in this study (male-to-female ratio, 1:1.71). The following LCQ items were highly correlated: embarrassment and interference with daily work, anxiety, and interference with overall life enjoyment/feeling of being fed up, interference with daily work and overall life enjoyment, interference with overall life enjoyment and feeling of being fed up, and feeling of being fed up and annoyance to partner/family/friends. The patterns of these correlations between LCQ items varied in males and females of different ages. The strongest interrelationship was observed in male patients aged >50 years old, which was similar to those in the validation cohort. CONCLUSION: The correlation patterns between cough-related symptoms vary significantly according to age and sex. Understanding the mechanisms underlying the development of cough-related symptoms may facilitate sex- and age-specific strategies for chronic cough.

HLA-DRB1 is associated with cefaclor-induced immediate hypersensitivity.

Background: Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity. Methods: Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site. Results: Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide significant at the 5 × 10-8 significance level. Cefaclor induced type I hypersensitivity was significantly associated with HLA-DRB1∗04:03 (OR 4.61 [95% CI 1.51-14.09], P < 0.002) and HLA-DRB1∗14:54 (OR 3.86 [95% CI 1.09-13.67], P < 0.002). Conclusion: LIMD1, HLA-DRB1∗04:03 and HLA-DRB1∗14:54 may affect susceptibility to cefaclor induced type I hypersensitivity. Further confirmative studies with a larger patient population should be performed to ascertain the role of HLA-DRB1 and LIMD1 in the development of cefaclor induced hypersensitivity.