Gastric Metastasis from Gastric-Type Mucinous Adenocarcinoma of Uterine Cervix: A Case Report.

Gastric metastasis (GM) from cervical cancer is extremely rare, and only a few cases have been reported in the English literature. Gastric-type mucinous adenocarcinomas (GAS) of the uterine cervix are rare. GAS is an aggressive cancer commonly found in advanced stages; however, GM has not been reported. This study presents a rare case of GM from GAS of the uterine cervix in a 61-year-old female and describes the radiological findings of both the GM and cervical mucinous adenocarcinoma. GM appeared as a poor enhancing submucosal mass. The cervical mucinous adenocarcinoma appeared as an infiltrating mass with poor contrast enhancement. It exhibited mildly high and low signal intensities on the diffusion-weighted image and apparent diffusion coefficient map, respectively. This case is extremely rare and challenging to diagnose; however, if cervical cancer is an human papillomavirus-independent GAS type and a submucosal lesion is found in the stomach, the possibility of metastasis with a pattern similar to our case could be considered.

Papillary Renal Cell Carcinoma in Transplanted Kidney and Xp11.2 Translocation/Transcription Factor E3-Rearranged Renal Cell Carcinoma in the Native Kidney: A Case Report.

Concomitant renal cell carcinomas (RCC) of both native and allograft kidneys are extremely rare, and only a few cases have been reported in the available English literature. A particularly rare variant within the adult population is the Xp11.2 translocation/transcription factor E3 (TFE3)-rearranged RCC. Although few case reports of TFE3-rearranged RCC have been reported in children who underwent kidney transplantation (KT), no case of adults with TFE3-rearranged RCC following KT has been reported. Herein, we presented the radiological and pathological findings of a rare metachronous papillary RCC in the allograft kidney and TFE3-rearranged RCC in the native kidney. The TFE3-rearranged RCC in the native kidney exhibited slow expansion in size over five years. Radiologically, it appeared as a slightly enhanced, lobulated mass on contrast-enhanced CT. MRI revealed high signal intensity on T1-weighted images and low signal intensity on T2-weighted images.

Relationship of computed tomography-based measurements with symptom perception and quality of life in patients with severe asthma.

BACKGROUND: Symptom perception and quality of life (QOL) are important domains for properly managing severe asthma. This study aimed to assess the relationship between airway structural and parenchymal variables measured using chest computed tomography (CT) and subjective symptom perception and QOL in patients with severe asthma enrolled in the Korean Severe Asthma Registry. METHODS: This study used CT-based objective measurements, including airway wall thickness (WT), hydraulic diameter, functional small airway disease (fSAD), and emphysematous lung (Emph), to assess their association with subjective symptom (cough, dyspnea, wheezing, and sputum) perception measured using the visual analog scale, and QOL measured by the Severe Asthma Questionnaire (SAQ). RESULTS: A total of 94 patients with severe asthma were enrolled in this study. The WT and fSAD% were significantly positively associated with cough and dyspnea, respectively. For QOL, WT and Emph% showed significant negative associations with the SAQ. However, there was no significant association between lung function and symptom perception or between lung function and QOL. CONCLUSION: Overall, WT, fSAD%, and Emph% measured using chest CT were associated with subjective symptom perception and QOL in patients with severe asthma. This study provides a basis for clarifying the clinical correlates of imaging-derived metrics and for understanding the mechanisms of respiratory symptom perception.

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.

Aspirin Challenge-Induced Genome-Wide DNA Methylation Profile of Peripheral Blood Lymphocytes in Aspirin-Exacerbated Respiratory Disease.

Genetic variation and epigenetic factors are thought to contribute to the development of hypersensitivity to aspirin. DNA methylation fluctuates dynamically throughout the day. To discover new CpG methylation in lymphocytes associated with aspirin-exacerbated respiratory disease (AERD), we evaluated changes in global CpG methylation profiles from before to after an oral aspirin challenge in patients with AERD and aspirin-tolerant asthma (ATA). Whole-genome CpG methylation levels of peripheral blood mononuclear cells were quantified with an Illumina 860K Infinium Methylation EPIC BeadChip array and then adjusted for inferred lymphocyte fraction (ILF) with GLINT and Tensor Composition Analysis. Among the 866,091 CpGs in the array, differentially methylated CpGs (DMCs) were found in 6 CpGs in samples from all 12 patients with asthma included in the study (AERD, n = 6; ATA, n = 6). DMCs were found in 3 CpGs in the 6 ATA samples and in 615 CpGs in the 6 AERD samples. A total of 663 DMCs in 415 genes and 214 intergenic regions differed significantly in the AERD compared with the ATA. In promoters, 126 CpG loci were predicted to bind to 38 transcription factors (TFs), many of which were factors already known to be involved in the pathogenesis of asthma and immune responses. In conclusion, we identified 615 new CpGs methylated in peripheral blood lymphocytes by oral aspirin challenge in AERD but not in ATA. These findings indicate that oral aspirin challenge induces epigenetic changes in ILFs, specifically in AERD patients, possibly via changes in TF binding, which may have epigenetic effects on the development of AERD.

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.

Functional Analysis of Membrane-Associated Scaffolding Tight Junction (TJ) Proteins in Tumorigenic Characteristics of B16-F10 Mouse Melanoma Cells.

Tight junction (TJ) proteins (Tjps), Tjp1 and Tjp2, are tight junction-associated scaffold proteins that bind to the transmembrane proteins of tight junctions and the underlying cytoskeleton. In this study, we first analyzed the tumorigenic characteristics of B16-F10 melanoma cells, including cell proliferation, migration, invasion, metastatic potential, and the expression patterns of related proteins, after the CRISPR-Cas9-mediated knockout (KO) of Tjp genes. The proliferation of Tjp1 and Tjp2 KO cells significantly increased in vitro. Other tumorigenic characteristics, including migration and invasion, were significantly enhanced in Tjp1 and Tjp2 KO cells. Zonula occludens (ZO)-associated protein Claudin-1 (CLDN-1), which is a major component of tight junctions and functions in controlling cell-to-cell adhesion, was decreased in Tjp KO cells. Additionally, Tjp KO significantly stimulated tumor growth and metastasis in an in vivo mouse model. We performed a transcriptome analysis using next-generation sequencing (NGS) to elucidate the key genes involved in the mechanisms of action of Tjp1 and Tjp2. Among the various genes affected by Tjp KO-, cell cycle-, cell migration-, angiogenesis-, and cell-cell adhesion-related genes were significantly altered. In particular, we found that the Ninjurin-1 (Ninj1) and Catenin alpha-1 (Ctnna1) genes, which are known to play fundamental roles in Tjps, were significantly downregulated in Tjp KO cells. In summary, tumorigenic characteristics, including cell proliferation, migration, invasion, tumor growth, and metastatic potential, were significantly increased in Tjp1 and Tjp2 KO cells, and the knockout of Tjp genes significantly affected the expression of related proteins.

Successful management of proteinuria in recurrent immunoglobulin A nephropathy after deceased donor kidney transplantation: A case report.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis, and recurrent IgAN is common after kidney transplantation (KT). Owing to the differences in various biopsy protocols and follow-ups in each study, the recurrence rate varies from 9.7% to 46%. Although the relapse rates are high, there is no definitive treatment for IgAN recurrence. METHODS: We present a case of successful management of proteinuria in recurrent IgAN after deceased donor KT. A 60-year-old man diagnosed with IgAN 20 years prior, who progressed to end-stage renal disease, underwent deceased donor KT 5 years prior and was admitted to our hospital with progressively increasing proteinuria. RESULTS: The pathological examination of the kidney biopsy specimen revealed recurrent IgAN. High-dose steroid treatment was initiated, and the patient was discharged while maintaining steroid treatment. However, outpatient follow-up showed that proteinuria did not decrease while steroids were maintained. Therefore, an angiotensin receptor blocker was administered after explaining its benefits to the patient. After the addition of angiotensin receptor blocker, proteinuria continued to decrease. CONCLUSION: This case report highlights the importance of using renin-angiotensin system inhibitors with supportive care in cases of suspected of recurrent IgAN after KT. It also emphasizes the need to prescribe renin-angiotensin system inhibitors when steroid therapy is unsuccessful in cases of recurrent IgAN after KT.

PD-L1 and PD-1 Expression in Early Stage Uterine Endometrioid Carcinoma.

BACKGROUND/AIM: Immune checkpoint inhibitors (ICI) and tumor-infiltrating lymphocytes (TILs) for cancer treatment in clinical oncology have revolutionized patient care. However, no gold standard exists for the criteria of analytical validity of TILs of different types of cancer. MATERIALS AND METHODS: Clinicopathological data from 60 patients with endometrioid carcinoma (EC) who had undergone surgical treatment at the Gyeongsang National University Hospital between January 2002 and December 2009, were investigated. The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PDL1) expression levels were characterized by immunohistochemical staining patterns, and the interpretations derived from machine learning morphometric analysis (Genie) and the pathologists' assessments were compared. In solid tumors, pathologists assessed the proportion of positive cells in each core of the tissue microarray. For Genie, the proportion of positive cells in the entire core and the number of positive cells per 1 mm2 were used. RESULTS: Both the pathologists and Genie identified the same trend in association with tumor size, with significant differences (p=0.026, p=0.033). Genie expression showed a significant association with PD1 expression, and pathologists identified a significant association with PDL1 expression in immune cells. CONCLUSION: The PD1 expression levels identified in immune cells of EC specimens were similar between the pathologists and Genie, suggesting that there is little resistance to the introduction of morphometric analysis. To our knowledge, this is the first study to introduce and validate machine learning as an integrated method for predicting prognosis and treatment based on PD1 expression in EC tumor microenvironments.

Risk of asthma and/or wheezing in obese individuals with or without metabolic syndrome: From the Korea National Health and Nutrition Examination Survey data.

Introduction: Obesity increases the risk of asthma; however, whether metabolic syndrome (MS), with obesity being one of its five components, is also associated with increased asthma risk remains unclear. Objective: To investigate the association between the risk of asthma and obesity, MS, and each component of MS. Methods: We performed a cross-sectional study of 41,480 Korean adults by using data from the 2007-2016 Korean National Health and Nutrition Examination Survey. Asthma was defined as a history of physician-diagnosed asthma or wheezing sound within the past 12 months. Results: The adjusted odds ratio (OR) for asthma was significantly increased in participants with obesity (OR 1.30 [95% confidence interval {CI}, 1.27-1.33]; p < 0.0001) and MS (OR 1.23 [95% CI, 1.20-1.25]; p < 0.0001). Obesity and MS showed an additive effect (OR 1.38 [95% CI, 1.34-1.41]; p < 0.001), followed by obesity(+)MS(-) (OR 1.28 [95% CI, 1.25-1.31]; p < 0.001) and obesity(-)MS(+) (OR 1.14 [95% CI, 1.10-1.18]; p < 0.001). Among each metabolic component, only abdominal obesity (OR 1.28 [95% CI, 1.24-1.32]; p < 0.001) and hypertension (OR 1.16 [95% CI, 1.12-1.20]; p < 0.001) significantly increased the risk of asthma. Unlike the female patients (OR 1.39 [95% CI, 1.35-1.43]; p < 0.001), having MS showed a lower risk of asthma in the male patients (OR 0.79 [95% CI, 0.75-0.82]; p < 0.001). Conclusion: The risk of asthma was highest when both obesity and MS were present, followed by obesity alone and MS alone. Abdominal obesity and hypertension were associated with an increased asthma risk, and there was a sex difference that MS lowered the risk of asthma in Korean male patients.

A comparison of treatment response to biologics in asthma-COPD overlap and pure asthma: Findings from the PRISM study.

Background: Despite the increasing use of biologics in severe asthma, there is limited research on their use in asthma-chronic obstructive pulmonary disease overlap (ACO). We compared real-world treatment responses to biologics in ACO and asthma. Methods: We conducted a multicenter, retrospective, cohort study using data from the Precision Medicine Intervention in Severe Asthma (PRISM). ACO was defined as post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and a smoking history of >10 pack-years. Physicians selected biologics (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) based on each United States Food & Drug Administration (FDA) approval criteria. Results: After six-month treatment with biologics, both patients with ACO (N = 13) and asthma (N = 81) showed positive responses in FEV1 (10.69 ± 17.17 vs. 11.25 ± 12.87 %, P = 0.652), Asthma Control Test score (3.33 ± 5.47 vs. 5.39 ± 5.42, P = 0.290), oral corticosteroid use (-117.50 ± 94.38 vs. -115.06 ± 456.85 mg, P = 0.688), fractional exhaled nitric oxide levels (-18.62 ± 24.68 vs. -14.66 ± 45.35 ppb, P = 0.415), sputum eosinophils (-3.40 ± 10.60 vs. -14.48 ± 24.01 %, P = 0.065), blood eosinophils (-36.47 ± 517.02 vs. -363.22 ± 1294.59, P = 0.013), and exacerbation frequency (-3.07 ± 4.42 vs. -3.19 ± 5.11, P = 0.943). The odds ratio for exacerbation and time-to-first exacerbation showed no significant difference after full adjustments, and subgroup analysis according to biologic type was also showed similar results. Conclusions: Biologics treatment response patterns in patients with ACO and asthma were comparable, suggesting that biologics should be actively considered for ACO patients as well.

FcRn Expression in Endometrial Cancer and Its Association with Clinicopathologic Features.

BACKGROUND: Endometrial cancer (EC) has robust molecular diagnostic evidence that correlates well with prognosis. In various types of cancers, FcRn has been identified as an early marker for prognosis. This study aims to assess FcRn expression and its association with clinicopathological features in endometrial cancer. MATERIALS AND METHODS: We employed a tissue microarray (TMA) from a retrospective cohort of 41 patients diagnosed with endometrioid endometrial cancer post hysterectomy between January 2002 and December 2009 at Gyeongsang National University Hospital. Relevant clinical data collection for the cohort involved reviewing patients' electronic medical charts. FcRn expression in microarrays of patient EC tissue was examined in conjunction with clinicopathologic data. Experiments, including siRNA knock-down, PCR mRNA semiquantification, Western blot, and confluence change tests, were conducted on the Ishikawa cell line. RESULTS: The overall FcRn expression rate in EC patients was 41.8%. FIGO stage showed a statistically significant relationship with FcRn expression, while age, lymphovascular invasion, myometrial invasion, and tumor size had no effect. In endometrioid cancer cells of FIGO stage IA, FcRn was less frequently expressed than in other high-staged EC patients (p = 0.021). In experiments on the Ishikawa cell line, the siRNA knock-down group exhibited quantitatively lower FCGRT mRNA expression and lower FcRn protein signal compared to the scrambled RNA control group. The change in confluence over time measured at three hotspots did not show a significant difference between groups. CONCLUSIONS: To the best of our knowledge, this study represents the initial assessment of FcRn expression in endometrioid EC samples. FcRn expression was significantly associated with the FIGO stage. Ishikawa cell line proliferation did not significantly change in response to decreased FcRn expression. Further studies are needed to elucidate FcRn expression in EC as a potential molecular parameter.

The Role of Human Endogenous Retrovirus (HERV)-K119 env in THP-1 Monocytic Cell Differentiation.

Human endogenous retrovirus (HERV)-K was reportedly inserted into the human genome millions of years ago and is closely related to various diseases, including cancer and immune regulation. In our previous studies, CRISPR-Cas9-enabled knockout (KO) of the HERV-K env gene was found to potentially reduce cell proliferation, cell migration, and invasion in colorectal and ovarian cancer cell lines. The immune response involves the migration and invasion of cells and is similar to cancer; however, in certain ways, it is completely unlike cancer. Therefore, we induced HERV-K119 env gene KO in THP-1, a monocytic cell that can be differentiated into a macrophage, to investigate the role of HERV-K119 env in immune regulation. Cell migration and invasion were noted to be significantly increased in HERV-K119 env KO THP-1 cells than in MOCK, and these results were contrary to those of cancer cells. To identify the underlying mechanism of HERV-K119 env KO in THP-1 cells, transcriptome analysis and cytokine array analysis were conducted. Semaphorin7A (SEMA7A), which induces the production of cytokines in macrophages and monocytic cells and plays an important role in immune effector cell activation during an inflammatory immune response, was significantly increased in HERV-K119 env KO THP-1 cells. We also found that HERV-K119 env KO THP-1 cells expressed various macrophage-specific surface markers, suggesting that KO of HERV-K119 env triggers the differentiation of THP-1 cells from monocytic cells into macrophages. In addition, analysis of the expression of M1 and M2 macrophage markers showed that M1 macrophage marker cluster of differentiation 32 (CD32) was significantly increased in HERV-K119 env KO cells. These results suggest that HERV-K119 env is implicated in the differentiation of monocytic cells into M1 macrophages and plays important roles in the immune response.

Perilipin1 Expression as a Prognostic Factor in Patients with Squamous Cell Carcinoma of the Lung.

Perilipin (PLIN) is a major structural protein located on the surface of lipid droplets. PLIN plays an important role in human metabolism and is associated with metabolic diseases, such as obesity, diabetes, hypertension, and endocrine disorders. The dysregulation of lipid metabolism is one of the most prominent metabolic changes observed in cancers. Therefore, the PLIN protein family has recently attracted attention owing to its role in lipid metabolism and cancer. To date, no studies have addressed the association between the prognosis of lung cancer and PLIN1 expression. For the first time, we found that high PLIN1 expression was significantly correlated with worse disease-free survival (DFS) in lung squamous cell carcinoma (SCC). We examined PLIN1 expression by the immunohistochemical analysis of surgical lung SCC specimens obtained from 94 patients. We analyzed the correlation between PLIN1 expression, clinicopathological data, and patient survival, using a chi-squared test, Kaplan-Meier analysis with log-rank tests, and the multivariate Cox proportional hazards regression test. High PLIN1 expression was significantly correlated with lower DFS in the Kaplan-Meier analysis and the multivariate Cox proportional hazards regression model. High PLIN1 expression was significantly correlated with worse prognosis in lung SCC.

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. The cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939).

Effect of White Noise on Pain Response, Heart Rate, and Oxygen Saturation During Heel Puncture in Premature Infants: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to investigate the effect of white noise on pain response, heart rate, and oxygen saturation during heel puncture in premature infants. METHODS: A randomized, controlled, pretest-posttest design was used. The participants were premature infants admitted to the neonatal intensive care unit of a university hospital in Gyeonggi Province. Sixty premature infants were assigned to either an experimental (n = 30) or control (n = 30) group. The experimental group was exposed to white noise during heel puncture, and the measured variables were pain response, heart rate, and oxygen saturation. The data were analyzed using the independent t test, chi-squared test, and analysis of covariance. RESULTS: Premature infants in the experimental group had a lower pain response and heart rate than the control group (F = 81.26, P < .01; F = 7.05, P = .01), and higher oxygen saturation than the control group (F = 4.76, P = .03). CONCLUSION: These results demonstrated that the white noise intervention is an effective nursing intervention to reduce the pain response and stabilize heart rate and oxygen saturation in premature infants during heel puncture.

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.

A smartphone-based application for cough counting in patients with acute asthma exacerbation.

Background: While tools exist for objective cough counting in clinical studies, there is no available tool for objective cough measurement in clinical practice. An artificial intelligence (AI)-based cough count system was recently developed that quantifies cough sounds collected through a smartphone application. In this prospective study, this AI-based cough algorithm was applied among real-world patients with an acute exacerbation of asthma. Methods: Patients with an acute asthma exacerbation recorded their cough sounds for 7 days (2 consecutive hours during awake time and 5 consecutive hours during sleep) using CoughyTM smartphone application. During the study period, subjects received systemic corticosteroids and bronchodilator to control asthma. Coughs collected by application were counted by both the AI algorithm and two human experts. Subjects also provided self-measured peak expiratory flow rate (PEFR) and completed other outcome assessments [e.g., cough symptom visual analogue scale (CS-VAS), awake frequency, salbutamol use] to investigate the correlation between cough and other parameters. Results: A total of 1,417.6 h of cough recordings were obtained from 24 asthmatics (median age =39 years). Cough counts by AI were strongly correlated with manual cough counts during sleep time (rho =0.908, P<0.001) and awake time (rho =0.847, P<0.001). Sleep time cough counts were moderately to strongly correlated with CS-VAS (rho =0.339, P<0.001), the frequency of waking up (rho =0.462, P<0.001), and salbutamol use at night (rho =0.243, P<0.001). Weak-to-moderate correlations were found between awake time cough counts and CS-VAS (rho =0.313, P<0.001), the degree of activity limitation (rho =0.169, P=0.005), and salbutamol use at awake time (rho =0.276, P<0.001). Neither awake time nor sleep time cough counts were significantly correlated with PEFR. Conclusions: The strong correlation between cough counts using the AI-based algorithm and human experts, and other indicators of patient health status provides evidence of the validity of this AI algorithm for use in asthma patients experiencing an acute exacerbation. Study findings suggest that CoughyTM could be a novel solution for objectively monitoring cough in a clinical setting.

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

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Bacterial Etiology in Subacute Cough.

Although postinfectious etiology is the most common cause of subacute cough, there are insufficient data on the epidemiology of associated bacterial infections. We aimed to identify the etiology of bacterial detection in subjects with subacute cough. A multicenter prospective observational study of 142 patients with postinfectious subacute cough was performed between August 2016 and December 2017 in Korea. We obtained 2 nasal swabs from each patient and used a multiplex bacterial polymerase chain reaction (PCR) kit that simultaneously detects Bordetella pertussis, Chlamydophila pneumoniae, Haemophilus influenzae, Legionella pneumophilia, Mycoplasma pneumoniae, and Streptococcus pneumoniae. About 29% (n = 41) of patients with subacute cough were positive for bacterial PCR in nasal swabs. The most common bacteria detected by bacterial PCR was H. influenzae (n = 19, 13.4%), followed by S. pneumoniae (n = 18, 12.7%), B. pertussis (n = 7, 4.9%), M. pneumoniae (n = 3, 2.1%), L. pneumophilia (n = 2, 1.4%), and C. pneumoniae (n = 1, 0.7%). Nine patients had dual positivity for the PCR. In conclusion, bacterial PCR was positive in the nasal swabs of about 29% of subjects with subacute cough, including 5% of positive PCR results for B. pertussis.