Inappropriate Peak Inspiratory Flow Rate in the Patients with Stable Chronic Obstructive Pulmonary Disease in Korea.

Background: Inhalation therapy efficacy hinges on proper peak inspiratory flow rate (PIFR) attainment, yet the prevalence of inappropriate PIFR among patients with chronic obstructive pulmonary disease (COPD) remains unstudied in Korea. This study aimed to assess the prevalence of inappropriate PIFR, its correlation with COPD assessment test (CAT) scores, and factors associated with suboptimal PIFR. Methods: We enrolled 108 patients with COPD who had been using the same inhaler for at least one year without exacerbations. PIFR was measured using an inspiratory flow meter (In-Check™ DIAL G16). Demographic, clinical, pulmonary function, and CAT score data were collected. Inappropriate was defined as PIFR < 60L/min for dry power inhaler (DPI) users or > 90L/min for aerosol device users. Results: The cohort comprised 87 (80.6%) men, mean age 71.0 ± 8.5 years, with mean post-bronchodilator forced expiratory volume in one second of 69.1 ± 1.8% predicted. Twenty-nine (26.9%) used aerosol devices, 76 (70.4%) used DPIs, and three (2.8%) used both. Inappropriate PIFRs were found in 17.2% of aerosol device users and 42.1% of DPI users. CAT scores were significantly higher in inappropriate PIFR group than appropriate PIFR group (11.2 ± 7.7 vs 7.5 ± 4.9, P = 0.003). In DPI users, female, shorter height, lower body weight and MVV (maximal voluntary ventilation) were associated with inappropriate PIFR. Conclusions: Prevalence of inappropriate PIFR among patients with COPD is 17.2% for aerosol device users and 42.1% for DPI users. Suboptimal PIFR correlates with female gender, shorter stature, lower weight and MVV in DPI users.

Pneumonia Prevalence Upon Chest Radiography According to Vaccination Status Among Patients Under 50 Years of Age With Coronavirus Disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination is effective in preventing the disease transmission and progression. However, the relatively mild disease course of the omicron variant and the decrease in antibodies over time after vaccination raise questions about the effectiveness of vaccination, especially in young people. We compared the prevalence of pneumonia and chest X-ray severity score according to vaccination status among patients < 50 years old with COVID-19. METHODS: From January 17 to March 17, 2022, 579 patients with COVID-19, who were < 50 years old and had a known vaccination history in our institution, were all included in this study. All patients underwent initial chest radiography, and follow-up chest radiographs were obtained every two days until discharge. Pneumonia was scored from the radiographs using the Brixia scoring system. The scores of the six lung zones were added for a total score ranging from 0 to 18. Patients were divided into four groups according to 10-year age intervals. Differences between groups were analyzed using the χ² or Fisher's exact tests for categorical variables and the Kruskal-Wallis test or analysis of variance for continuous variables. RESULTS: Among patients aged 12-19 years, the prevalence of pneumonia did not differ depending on vaccination status (non-vaccinated vs. vaccinated, 1/47 [2.1%] vs. 1/18 [5.6%]; P = 0.577). Among patients in their 20s, the prevalence of pneumonia was significantly higher among non-vaccinated patients than among vaccinated patients (8/28, 28.6% vs. 7/138, 5.1%, P < 0.001), similar to patients in their 40s (32/52 [61.5%] vs. 18/138 [13.0%]; P < 0.001). The chest X-ray severity score was also significantly higher in non-vaccinated patients than that in vaccinated patients in their 20s to their 40s (P < 0.001), but not among patients aged 12-19 years (P = 0.678). CONCLUSION: In patients aged 20-49 years, vaccinated patients had a significantly lower prevalence of pneumonia and chest X-ray severity score than non-vaccinated patients.

Associations of personal urinary volatile organic compounds and lung function in children.

BACKGROUND: We investigated the correlation between urine VOC metabolites and airway function in children exposed to anthropogenic volatile organic compounds (VOCs), notable pollutants impacting respiratory health. METHODS: Out of 157 respondents, 141 completed skin prick tests, spirometry, IOS, and provided urine samples following the International Study of Asthma and Allergies in Childhood (ISAAC)-related questions. Allergic sensitization was assessed through skin prick tests, and airway functions were evaluated using spirometry and impulse oscillometry (IOS). Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) was recorded and FEV1/FVC ratio was calculated. Airway mechanics parameters including respiratory resistance at 5 Hz (Rrs5) mean respiratory resistance between 5 Hz and 20 Hz (Rrs5-20), were also recorded. Urine concentrations of metabolites of benzene, ethylbenzene, toluene, xylene, styrene, formaldehyde, carbon-disulfide were analyzed by gas chromatography/tandem mass spectroscopy. RESULTS: The median age at study participation was 7.1 (SD 0.3) years. Muconic acid (benzene metabolites) and o-methyl-hippuric acid (xylene metabolites) above medians were associated with a significant increase in Rrs5 (muconic acid: aß = 0.150, p = .002; o-methyl-hippuric acid: aß = 0.143, p = .023) and a decrease in FEV1/FVC (o-methyl-hippuric acid: aß = 0.054, p = .028) compared to those below median. No associations were observed for Rrs5-20 and FEV1 between the groups categorized as above and below the median (all parameter p values > .05). CONCLUSIONS: Elevated levels of benzene and xylene metabolites were associated with a significant increase in Rrs5 and a decrease in FEV1/FVC, related to increased resistance and restrictive lung conditions compared to individuals with concentrations below the median.

Functional Characterization of Gonadotropin-Releasing Hormone and Corazonin Signaling Systems in Pacific Abalone: Toward Reclassification of Invertebrate Neuropeptides.

INTRODUCTION: The proposed evolutionary origins and corresponding nomenclature of bilaterian gonadotropin-releasing hormone (GnRH)-related neuropeptides have changed tremendously with the aid of receptor deorphanization. However, the reclassification of the GnRH and corazonin (CRZ) signaling systems in Lophotrochozoa remains unclear. METHODS: We characterized GnRH and CRZ receptors in the mollusk Pacific abalone, Haliotis discus hannai (Hdh), by phylogenetic and gene expression analyses, bioluminescence-based reporter, Western blotting, substitution of peptide amino acids, in vivo neuropeptide injection, and RNA interference assays. RESULTS: Two Hdh CRZ-like receptors (Hdh-CRZR-A and Hdh-CRZR-B) and three Hdh GnRH-like receptors (Hdh-GnRHR1-A, Hdh-GnRHR1-B, and Hdh-GnRHR2) were identified. In phylogenetic analysis, Hdh-CRZR-A and -B grouped within the CRZ-type receptors, whereas Hdh-GnRHR1-A/-B and Hdh-GnRHR2 clustered within the GnRH/adipokinetic hormone (AKH)/CRZ-related peptide-type receptors. Hdh-CRZR-A/-B and Hdh-GnRHR1-A were activated by Hdh-CRZ (pQNYHFSNGWHA-NH2) and Hdh-GnRH (pQISFSPNWGT-NH2), respectively. Hdh-CRZR-A/-B dually coupled with the Gαq and Gαs signaling pathways, whereas Hdh-GnRHR1-A was linked only with Gαq signaling. Analysis of substituted peptides, [I2S3]Hdh-CRZ and [N2Y3H4]Hdh-GnRH, and in silico docking models revealed that the N-terminal amino acids of the peptides are critical for the selectivity of Hdh-CRZR and Hdh-GnRHR. Two precursor transcripts for Hdh-CRZ and Hdh-GnRH peptides and their receptors were mainly expressed in the neural ganglia, and their levels increased in starved abalones. Injection of Hdh-CRZ peptide into abalones decreased food consumption, whereas Hdh-CRZR knockdown increased food consumption. Moreover, Hdh-CRZ induced germinal vesicle breakdown in mature oocytes. CONCLUSION: Characterization of Hdh-CRZRs and Hdh-GnRHRs and their cognate peptides provides new insight into the evolutionary route of GnRH-related signaling systems in bilaterians.

Crustacean cardioactive peptide signaling system in the gastropod mollusk Pacific abalone.

Crustacean cardioactive peptide (CCAP) signaling systems have been characterized in a diverse range of protostomes, representatively in arthropods. The cyclic CX5C-type CCAP regulates various biological activities through CCAP receptors (CCAPRs), which are orthologous to neuropeptide S receptors (NPSRs) in deuterostomes. However, the CCAPRs of the lophotrochozoa remain poorly characterized; therefore, the relationship between the CCAP, NPS, and CX4C-type oxytocin/vasopressin (OT/VP) signaling systems is unclear. In this study, we identified a CCAP precursor and two CCAPR isoforms in the Pacific abalone (Haliotis discus hannai; Hdh). The Hdh-CCAP precursor was found to harbor three CX5C-type and one CX4C-type CCAPs. The Hdh-CCAPRs displayed homology with protostome CCAPRs and deuterostome NPSRs, having characteristics of the rhodopsin-type G protein-coupled receptors. Phylogenetic analysis showed that lophotrochozoan CCAPRs, including Hdh-CCAPRs, form a monophyletic group distinct from arthropod CCAPRs. Reporter assays demonstrated that all examined Hdh-CCAPs and insect CCAP-induced intracellular Ca2+ mobilization and cAMP accumulation in Hdh-CCAPR-expressing HEK293 cells, whereas none of the CCAP peptides inhibited the forskolin-stimulated cAMP signaling pathway even at micromolar concentrations. In silico ligand-receptor docking models showed that the N-terminal FCN motifs of Hdh-CCAPs are deeply inserted inside the binding pocket of Hdh-CCAPR, forming extensive hydrophobic interactions. In mature Pacific abalone, the transcripts for Hdh-CCAP precursor and Hdh-CCAPR were highly expressed in the neural ganglia compared to the peripheral tissues. Collectively, this study characterized the first CCAP signaling system linked to both Ca2+/PKC and cAMP/PKA signal transduction pathways in gastropod mollusks and gives insights into the evolutional origins of deuterostomian NPS and OT/VP signaling systems.

Outcomes of the electromagnetic navigation bronchoscopy using forceps for lung lesion suspected malignancy: A retrospective study.

Many studies have reported electromagnetic navigation bronchoscopy (ENB) diagnostic yields and the importance of size and computed tomography (CT) bronchus sign. This study aimed to determine the diagnostic yield of ENB alone, using forceps biopsy and cytology. We analyzed the factors associated with yield and complications according to gross specimen size. This retrospective study included patients who underwent ENB using forceps for suspected lung lesions on CT between January 2020 and December 2022 in South Korea. Factors related to the ENB diagnostic yield and complications were evaluated, and the impacts of gross specimen size and cytology were analyzed. A total of 276 patients were analyzed. The final diagnostic yield was 75.5% after excluding indeterminate cases. Sensitivity and specificity were 74.2% and 100%, respectively. Pneumothorax developed in 1.4% (4/276) of cases, with no grade 3 or higher bleeding. Univariable analysis showed that the number of biopsies and the size of the gross specimen were related to the diagnosis. Multivariable analyses showed that a larger lesion size on CT was a significant factor for diagnosis. The gross size of the specimens was not significantly associated with epinephrine use. ENB had acceptable diagnostic yield and safety for diagnosing lung lesions with suspected malignancy. Obtaining more tissue through biopsy may not increase bleeding or pneumothorax complications. Identifying patients with lesion characteristics, including CT bronchus sign, would help increase ENB diagnostic yield.

Efficacy of Second-Line Treatments in Chronic Urticaria Refractory to Standard Dose Antihistamines.

PURPOSE: The prevalence of chronic urticaria (CU) is increasing worldwide, and it imposes a major burden on patients. Few studies have evaluated the efficacy of second-line treatments of CU, particularly for patients being considered for costly third-line treatments such as omalizumab. We compared the efficacy and safety of second-line treatments of CU refractory to standard doses of nonsedating H1-antihistamines (nsAHs). METHODS: This 4-week, prospective, randomized, open-label trial divided patients into 4 treatment groups: 4-fold updosing of nsAHs, multiple combination of 4 nsAHs, switching to other nsAHs, and adjunctive H2-receptor antagonist. The clinical outcomes included urticaria control status, symptoms, and rescue medication use. RESULTS: This study included 109 patients. After 4 weeks of second-line treatment, urticaria was well-controlled, partly controlled, and uncontrolled in 43.1%, 36.7%, and 20.2% of patients, respectively. Complete control of CU was achieved in 20.4% of patients. Among the patients with high-dose nsAHs, the proportion with well-controlled status was higher compared to the patients who received standard doses (51.9% vs. 34.5%, P = 0.031). No significant difference was observed in the proportion of well-controlled cases between the updosing and combination treatment groups (57.7% vs. 46.4%, P = 0.616). However, increasing the dose of nsAHs 4-fold was associated with a higher rate of complete symptom control compared to multiple combination treatment with 4 nsAHs (40.0% vs. 10.7%, P = 0.030). Logistic regression analysis confirmed the higher efficacy of updosing of nsAHs for complete control of CU compared to the other treatment strategies (odds ratio, 0.180; P = 0.020). CONCLUSIONS: In patients with CU refractory to standard doses of nsAHs, both updosing of nsAHs 4-fold and multiple combination treatment with 4 nsAHs increased the rate of well-controlled cases without causing significant adverse effects. Updosing of nsAHs is more effective for complete CU control than combination treatment.

Stratification of Nontuberculous Mycobacterial Disease Risk in Type 2 Diabetes Based on Metformin Use: a Population-Based Cohort Study in South Korea.

In a 1:4 case-control matched analysis of data from a nationwide population-based cohort in South Korea, we evaluated whether metformin use mitigates the risk of nontuberculous mycobacterial disease in patients with type 2 diabetes. Multivariable analysis revealed no significant association of metformin use with a diminished risk for incident nontuberculous mycobacterial disease in patients with type 2 diabetes.

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

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

Dual Biomarker Combining DNA Damage Repair Gene Mutations and PD-L1 Expression for Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer.

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) improve long-term survival in advanced non-small cell lung cancer (NSCLC) and require robust predictive biomarkers for the selection of responders. This study investigated the optimal implementation of DNA damage repair (DDR) gene mutations to predict response to ICIs in real-world NSCLC patients. PATIENTS AND METHODS: We retrospectively reviewed 55 advanced NSCLC patients who had undergone targeted high-throughput sequencing and received ICIs. Patients with two or more DDR gene mutations were defined as DDR2 positive. RESULTS: The patients' median age was 68 (range=44-82) years, and 48 (87.3%) were men. Seventeen patients (30.9%) showed ≥50% high programmed death-ligand 1 (PD-L1) expression. Ten patients (18.2%) received an ICI-chemotherapy combination as first-line therapy, and 38 (69.1%) received ICI monotherapy as more than second-line therapy. Fourteen patients (25.5%) were DDR2-positive. The objective response rate of patients with DDR2-positive or PD-L1 ≥50% was 45.5%, and that of patients with DDR2-negative and PD-L1 <50% was 11.1% (p=0.007). In the PD-L1 low expression subgroup (<50%), patients with DDR2-positive had improved progression-free survival (PFS) and overall survival (OS) after ICIs compared to those with DDR2-negative (PFS: 5.8 vs. 1.9 months, p=0.026, OS: 14.4 vs. 7.2 months, p=0.078). DDR2-positive patients or those with PD-L1 ≥50% (24, 43.6%) had statistically significant improvement in PFS and OS after ICIs compared to DDR2-negative and those with PD-L1 <50% (PFS: 4.4 vs. 1.9 months, p=0.006, OS: 11.6 vs. 7.2 months, p=0.037). CONCLUSION: A dual biomarker combining DDR gene mutations and PD-L1 expression improves the prediction of response to ICIs in advanced NSCLC.

Type 2 Diabetes Mellitus- and Complication-Related Risk of Nontuberculous Mycobacterial Disease in a South Korean Cohort.

We aimed to investigate whether type 2 diabetes mellitus (T2DM) and diabetes-related complications constitute significant risk factors for nontuberculous mycobacterial (NTM) disease. Data from the National Health Insurance Service-National Sample Cohort (which represents 2.2% of the total South Korean population) recorded between 2007 and 2019 were extracted to establish the NTM-naive T2DM cohort (n = 191,218) and the 1:1 age- and sex-matched NTM-naive matched cohort (n = 191,218). Intergroup comparisons were performed to determine differences in the NTM disease risk of the two cohorts during the follow-up period. During median follow-up of 9.46 and 9.25 years, the incidence of NTM disease was 43.58/100,000 and 32.98/100,000 person-years in the NTM-naive T2DM and NTM-naive matched cohorts, respectively. Multivariable analysis showed that T2DM alone did not confer a significant risk for incident NTM disease, although T2DM with ≥2 diabetes-related complications significantly increased NTM disease risk (adjusted hazard ratio [95% confidence interval], 1.12 [0.99 to 1.27] and 1.33 [1.03 to 1.17], respectively). In conclusion, the presence of T2DM with ≥2 diabetes-related complications significantly increases the risk for NTM disease. IMPORTANCE We assessed whether patients with T2DM are at higher risk for incident NTM disease through analysis of NTM-naive matched cohorts from the data of a national population-based cohort which represents 2.2% of the total South Korean population. Although T2DM alone is not a statistically significant risk factor for NTM disease, T2DM significantly increases the risk of NTM disease in those with ≥2 diabetes-related complications. This finding suggested that patients with T2DM with a larger number of complications should be considered a high-risk group for NTM disease.

KAAACI Allergic Rhinitis Guidelines: Part 1. Update in Pharmacotherapy.

The prevalence of allergic rhinitis (AR) and the socioeconomic burden associated with the medical cost and quality of life (QOL) of AR have progressively increased. Therefore, practical guidelines for the appropriate management of AR need to be developed based on scientific evidence while considering the real-world environment, values, and preferences of patients and physicians. The Korean Academy of Asthma, Allergy and Clinical Immunology revised clinical guidelines of AR to address key clinical questions of the management of AR. Part 1 of the revised guideline covers the pharmacological management of patients with AR in Korea. Through a meta-analysis and systematic review, we made 4 recommendations for AR pharmacotherapy, including intranasal corticosteroid (INCS)/intranasal antihistamine (INAH) combination therapy, oral antihistamine/INCS combination therapy, leukotriene receptor antagonist treatment in AR patients with asthma, and prophylactic treatment for patients with pollen-induced AR. However, all recommendations are conditional because of the low or very low evidence of certainty. Well-designed and strictly executed randomized controlled trials are needed to measure and report appropriate outcomes.

Lipid Profiling of Pacific Abalone (Haliotis discus hannai) at Different Developmental Stages Using Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectrometry.

Pacific abalone (Haliotis discus hannai) is a commercially important mollusk; therefore, improvement of its growth performance and quality has been emphasized. During embryonic development, abalones undergo a series of distinct larval stages, including swimming veliger larvae, juveniles, and mature individuals, and their biomolecular composition varies depending on the developmental stage. Therefore, in the present study, we performed untargeted lipid profiling of abalone tissues at different developmental stages as well as the hemolymph of mature female and male abalones using ultrahigh-performance liquid chromatography-tandem mass spectrometry. These profiles can provide meaningful information to understand compositional changes in lipids through abalone metamorphosis and development. A total of 132 lipids belonging to 15 classes were identified from abalone tissues at different developmental stages. Moreover, 21 lipids belonging to 8 classes were identified from the hemolymph of mature abalones. All data were processed following strict criteria to provide accurate information. Triglycerides and phosphatidylcholines were the major lipid components identified in both tissues and hemolymph, accounting for, respectively, 27% and 15% of all lipids in tissues and, respectively, 24% and 38% of all lipids in the hemolymph. Of note, lysophosphatidylcholine was only detected in the tissues of mature abalones, paving the way for further analyses of abalone lipids based on developmental stages. The present findings offer novel insights into the lipidome of abalone tissues and hemolymph at different developmental stages, building a foundation for improving the efficiency and quality of abalone aquaculture.

Neutrophil-Lymphocyte Ratio and Monocyte-Lymphocyte Ratio According to the Radiologic Severity of Mycobacterium avium Complex Pulmonary Disease.

BACKGROUND: To date, no study has investigated whether the neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR) have a clinical value in Mycobacterium avium complex (MAC)-pulmonary disease (PD). METHODS: We aimed to assess whether the baseline NLR and MLR were different according to the severity of MAC-PD based on the radiologic classification by retrospectively analyzing 549 patients treated in a tertiary referral center in South Korea. RESULTS: Both NLR and MLR were significantly higher as 3.33 and 0.43 respectively in the fibrocavitary type, followed by 2.34 and 0.27 in the cavitary nodular bronchiectatic type and significantly lower as 1.88 and 0.23 in the non-cavitary nodular bronchiectatic type. CONCLUSION: The baseline NLR and MLR showed a distinct difference in accordance with the radiologic severity of MAC-PD.

Multiple tachykinins and their receptors characterized in the gastropod mollusk Pacific abalone: Expression, signaling cascades, and potential role in regulating lipid metabolism.

Tachykinin (TK) families, including the first neuropeptide substance P, have been intensively explored in bilaterians. Knowledge of signaling of TK receptors (TKRs) has enabled the comprehension of diverse physiological processes. However, TK signaling systems are largely unknown in Lophotrochozoa. This study identified two TK precursors and two TKR isoforms in the Pacific abalone Haliotis discus hannai (Hdh), and characterized Hdh-TK signaling. Hdh-TK peptides harbored protostomian TK-specific FXGXRamide or unique YXGXRamide motifs at the C-termini. A phylogenetic analysis showed that lophotrochozoan TKRs, including Hdh-TKRs, form a monophyletic group distinct from arthropod TKRs and natalisin receptor groups. Although reporter assays demonstrated that all examined Hdh-TK peptides activate intracellular cAMP accumulation and Ca2+ mobilization in Hdh-TKR-expressing mammalian cells, Hdh-TK peptides with N-terminal aromatic residues and C-terminal FXGXRamide motifs were more active than shorter or less aromatic Hdh-TK peptides with a C-terminal YXGXRamide. In addition, we showed that ligand-stimulated Hdh-TKRs mediate ERK1/2 phosphorylation in HEK293 cells and that ERK1/2 phosphorylation is inhibited by PKA and PKC inhibitors. In three-dimensional in silico Hdh-TKR binding modeling, higher docking scores of Hdh-TK peptides were consistent with the lower EC50 values in the reporter assays. The transcripts for Hdh-TK precursors and Hdh-TKR were highly expressed in the neural ganglia, with lower expression levels in peripheral tissues. When abalone were starved for 3 weeks, Hdh-TK1 transcript levels, but not Hdh-TK2, were increased in the cerebral ganglia (CG), intestine, and hepatopancreas, contrasting with the decreased lipid content and transcript levels of sterol regulatory element-binding protein (SREBP). At 24 h post-injection in vivo, the lower dose of Hdh-TK1 mixture increased SREBP transcript levels in the CG and hepatopancreas and accumulative food consumption of abalone. Higher doses of Hdh-TK1 and Hdh-TK2 mixtures decreased the SREBP levels in the CG. When Hdh-TK2-specific siRNA was injected into abalone, intestinal SREBP levels were significantly increased, whereas administration of both Hdh-TK1 and Hdh-TK2 siRNA led to decreased SREBP expression in the CG. Collectively, our results demonstrate the first TK signaling system in gastropod mollusks and suggest a possible role for TK peptides in regulating lipid metabolism in the neural and peripheral tissues of abalone.

Phenotyping COPD Patients with Emphysema Distribution Using Quantitative CT Measurement; More Severe Airway Involvement in Lower Dominant Emphysema.

Purpose: We explored the differences in clinical manifestations of COPD patients regarding emphysema distribution along with evidence of airway involvement in chest computed tomography (CT) scans. Patients and Methods: The patients were divided into three groups according to the emphysema distribution: the upper dominant (UD), lower dominant (LD), and homogeneous (HD) groups. Airway wall thickness was quantitatively measured and the presence of bronchiectasis and/or bronchial wall thickening (BE/BWT) was visually assessed. Baseline characteristics including the evidence of airway involvement and long-term outcomes were compared among the three groups. Non-severe patients of each group were first treated with 3 months of ICS/LABA combination after 2 weeks of wash-out period and lung functions before and after the treatment were compared. Results: Of the 425 patients, 141 were in the UD, 107 in LD, and 177 in HD. The LD had more severe airway obstruction with lower emphysema index (EI) than the UD (LD vs UD; FEV1, 49.5-14.9 vs 54.6-16.5; EI, 21.0 [IQR: 14.0-33.1] vs 26.3 [IQR: 15.8-39.0]). The LD showed thicker airways (higher WA% and Pi10) and more severe air trapping (higher RV and RV/TLC) than UD. A larger proportion of patients in LD had BE/BWT (35.5% in LD vs 11.3% in UD). In LD, more patients experienced acute exacerbations and the time to first exacerbation was shorter than UD. Non-severe patients in LD treated with 3 months of ICS/LABA combined inhalers showed a notable reduction of RV than UD (LD vs UD; -531.1-936.5 vs -86.5-623.5). Conclusion: The LD showed a more prominent airway involvement than UD, which may cause more frequent exacerbations and a marked reduction of RV after the ICS/LABA combination treatment in LD. Phenotyping of the COPD patients using quantitatively measured emphysema distribution would be useful for predicting treatment response and exacerbation.

The burden of symptomatic patients with chronic spontaneous urticaria: a real-world study in Korea.

BACKGROUND/AIMS: Chronic spontaneous urticaria (CSU) poses a considerable burden both on the quality of life (QoL) of individual patients and on healthcare systems. Real­world data evaluating the disease burden of CSU are limited in this country. This study evaluated the disease burden and healthcare resource utilization (HRU) among symptomatic CSU patients. METHODS: This multicenter, noninterventional, retrospective, and cross-sectional study assessed CSU patients symptomatic for more than 6 months despite step-wise H1-antihistamine medications. Primary outcomes included Urticaria Activity Score over 7 days (UAS7) and Chronic Urticaria QoL scale (CU-QoL). Secondary outcomes included EuroQol 5-Dimension 5-Level (EQ-5D-5L), Dermatology Life Quality Index (DLQI), association of disease activity with QoL, medications used for the past 6 months, and HRU. RESULTS: Five hundred patients with CSU were enrolled. Mean disease duration was 3.7 years. Based on UAS7, 22.2% of patients were in well-controlled status and 31.2%, 28.4%, and 18.2% of them had mild, moderate, and severe disease, respectively. Mean CU-QoL and DLQI scores were 57.5 ± 29.7 and 10.2 ± 7.6, respectively, while the EQ-5D-5L utility score was 0.8 ± 0.2. H1-antihistamines were prescribed to 95% of patients, while omalizumab was prescribed to 33% of patients. Most patients (98%) had outpatient visits in the past 6 months. Negative correlations were noted between UAS7 and CU-QoL, EQ-5D-5L, EQ-5D-5L visual analog scale scores, but a positive correlation was noted with DLQI score (p < 0.001 for all). The number of outpatient department visits increased with disease activity (p = 0.001). CONCLUSION: CSU affects QoL, leading to increased HRU, particularly in patients with severe disease.

Functional analysis of LFRFamide signaling in Pacific abalone, Haliotis discus hannai.

The invertebrate LFRFamide (LFRFa) and short neuropeptide F (sNPF), consisting of 6 to 10 amino acids, are orthologs for bilaterian NPF/Y, which consist of 36 to 40 amino acids. Recently, a molluscan G protein-coupled receptor (GPCR) for NPF was characterized in Pacific abalone (Haliotis discus hannai). To address the functional evolutionary route of the invertebrate LFRFa and NPF signaling system, in this study, we identified cDNAs encoding LFRFa precursors and the sNPF receptor (Hdh-sNPFR) in Pacific abalone. Four LFRFa mature peptides with 6 or 7 amino acids were predicted: GSLFRFa, GGLFRFa, GTLFRFa, and GSTLFRFa. Hdh-sNPFR was identified as a classical rhodopsin-like GPCR and classified into a molluscan sNPFR group. In HEK293 cells, Hdh-sNPFR was mainly localized in the cell membranes and internalized in the cytoplasm following treatment with LFRFa peptides. Reporter assays demonstrated that LFRFa peptides inhibit forskolin-stimulated cAMP accumulation in Hdh-sNPFR-expressing HEK293 cells. LFRFa precursor and Hdh-sNPFR transcripts were more strongly expressed in the cerebral and pleural-pedal ganglia of Pacific abalone than in the peripheral tissues such as the ovary, gills, intestine, and hepatopancreas. The levels of LFRFa transcripts in the ovary, intestine, and hepatopancreas were significantly higher in mature female abalone than in immature females. Injection of LFRFa induced the egg release and spawning behavior of mature abalone, but suppressed food intake. These results suggest that LFRFa peptides are endogenous ligands for Hdh-sNPFR involved in food intake and reproduction through a Gαi-protein dependent signaling pathway.

Prescription Patterns of Oral Corticosteroids for Asthma Treatment and Related Asthma Phenotypes in University Hospitals in Korea.

PURPOSE: Oral corticosteroids (OCSs) are frequently prescribed for asthma management despite their adverse effects. An understanding of the pattern of OCS treatment is required to optimize asthma treatment and reduce OCS usage. This study evaluated the prescription patterns of OCSs in patients with asthma. METHODS: This is a retrospective multicenter observational study. We enrolled adult (≥18 years) patients with asthma who had been followed up by asthma specialists in 13 university hospitals for ≥3 years. Lung function tests, the number of asthma exacerbations, and prescription data, including the days of supply and OCS dosage, were collected. The clinical characteristics of OCS-dependent and exacerbation-prone asthmatic patients were evaluated. RESULTS: Of the 2,386 enrolled patients with asthma, 27.7% (n = 660) were OCS users (the median daily dose of OCS was 20 mg/day prednisolone equivalent to a median of 14 days/year). OCS users were more likely to be female, to be treated at higher asthma treatment steps, and to show poorer lung function and more frequent exacerbations in the previous year than non-OCS users. A total of 88.0% of OCS users were treated with OCS burst with a mean dose of 21.6 ± 10.2 mg per day prednisolone equivalent to 7.8 ± 3.2 days per event and 2.4 times per year. There were 2.1% (51/2,386) of patients with OCS-dependent asthma and 9.5% (227/2,386) with exacerbation-prone asthma. These asthma phenotypes were consistent over the 3 consecutive years in 47.1% of OCS-dependent asthmatic patients and 34.4% of exacerbation-prone asthmatic patients when assessed annually over the 3-year study period. CONCLUSIONS: We used real-world data from university hospitals in Korea to describe the OCS prescription patterns and relievers in asthma. Novel strategies are required to reduce the burden of OCS use in patients with asthma.