Purpose: Methacholine bronchial provocation tests (MBPTs) are commonly used to assess airway hyperresponsiveness, but some patients show no significant response. This study aimed to compare the clinical characteristics of asthmatic patients based on their sensitivity to MBPTs. Methods: We conducted a retrospective cross-sectional study involving adult asthmatic patients from 6 university hospitals in South Korea. Patients were categorized into 2 groups: those with MBPT sensitivity (the provocative concentration of methacholine that leads to a 20% reduction in forced expiratory volume in 1 second [PC20]≤ 16 mg/mL) and those with lower sensitivity (PC 20 > 16 mg/mL). Clinical characteristics were compared between the 2 groups. Results: Among 346 patients, 213 had PC 20 ≤ 16 mg/mL and 133 had PC 20 > 16 mg/mL. The PC20> 16 mg/mL group had a higher prevalence of late-onset asthma (P= 0.024) and obesity (P= 0.045). While no significant differences in immunoglobulin E (≥ 200 IU/mL) were found, the PC 20 ≤ 16 mg/mL group had greater T2-high inflammation, such as elevated eosinophil counts and fractional exhaled nitric oxide (P< 0.001 and P= 0.004, respectively). Asthma exacerbations requiring emergency visits or hospitalizations were more frequent in the PC 20 > 16 mg/mL group, despite a lower proportion of patients on higher-step treatments according to Global Initiative for Asthma guidelines. Conclusion Asthmatic patients with PC 20 > 16 mg/mL tend to present with late-onset asthma, less T2-high inflammation, and higher rates of asthma exacerbations. Further studies are needed to clarify the clinical features of asthma patients with PC 20 > 16 mg/mL and assess the long-term significance of these findings.

Purpose: Methacholine bronchial provocation tests (MBPTs) are commonly used to assess airway hyperresponsiveness, but some patients show no significant response. This study aimed to compare the clinical characteristics of asthmatic patients based on their sensitivity to MBPTs. Methods: We conducted a retrospective cross-sectional study involving adult asthmatic patients from 6 university hospitals in South Korea. Patients were categorized into 2 groups: those with MBPT sensitivity (the provocative concentration of methacholine that leads to a 20% reduction in forced expiratory volume in 1 second [PC20]≤ 16 mg/mL) and those with lower sensitivity (PC 20 > 16 mg/mL). Clinical characteristics were compared between the 2 groups. Results: Among 346 patients, 213 had PC 20 ≤ 16 mg/mL and 133 had PC 20 > 16 mg/mL. The PC20> 16 mg/mL group had a higher prevalence of late-onset asthma (P= 0.024) and obesity (P= 0.045). While no significant differences in immunoglobulin E (≥ 200 IU/mL) were found, the PC 20 ≤ 16 mg/mL group had greater T2-high inflammation, such as elevated eosinophil counts and fractional exhaled nitric oxide (P< 0.001 and P= 0.004, respectively). Asthma exacerbations requiring emergency visits or hospitalizations were more frequent in the PC 20 > 16 mg/mL group, despite a lower proportion of patients on higher-step treatments according to Global Initiative for Asthma guidelines. Conclusion Asthmatic patients with PC 20 > 16 mg/mL tend to present with late-onset asthma, less T2-high inflammation, and higher rates of asthma exacerbations. Further studies are needed to clarify the clinical features of asthma patients with PC 20 > 16 mg/mL and assess the long-term significance of these findings.

Purpose: Methacholine bronchial provocation tests (MBPTs) are commonly used to assess airway hyperresponsiveness, but some patients show no significant response. This study aimed to compare the clinical characteristics of asthmatic patients based on their sensitivity to MBPTs. Methods: We conducted a retrospective cross-sectional study involving adult asthmatic patients from 6 university hospitals in South Korea. Patients were categorized into 2 groups: those with MBPT sensitivity (the provocative concentration of methacholine that leads to a 20% reduction in forced expiratory volume in 1 second [PC20]≤ 16 mg/mL) and those with lower sensitivity (PC 20 > 16 mg/mL). Clinical characteristics were compared between the 2 groups. Results: Among 346 patients, 213 had PC 20 ≤ 16 mg/mL and 133 had PC 20 > 16 mg/mL. The PC20> 16 mg/mL group had a higher prevalence of late-onset asthma (P= 0.024) and obesity (P= 0.045). While no significant differences in immunoglobulin E (≥ 200 IU/mL) were found, the PC 20 ≤ 16 mg/mL group had greater T2-high inflammation, such as elevated eosinophil counts and fractional exhaled nitric oxide (P< 0.001 and P= 0.004, respectively). Asthma exacerbations requiring emergency visits or hospitalizations were more frequent in the PC 20 > 16 mg/mL group, despite a lower proportion of patients on higher-step treatments according to Global Initiative for Asthma guidelines. Conclusion Asthmatic patients with PC 20 > 16 mg/mL tend to present with late-onset asthma, less T2-high inflammation, and higher rates of asthma exacerbations. Further studies are needed to clarify the clinical features of asthma patients with PC 20 > 16 mg/mL and assess the long-term significance of these findings.

Purpose: Methacholine bronchial provocation tests (MBPTs) are commonly used to assess airway hyperresponsiveness, but some patients show no significant response. This study aimed to compare the clinical characteristics of asthmatic patients based on their sensitivity to MBPTs. Methods: We conducted a retrospective cross-sectional study involving adult asthmatic patients from 6 university hospitals in South Korea. Patients were categorized into 2 groups: those with MBPT sensitivity (the provocative concentration of methacholine that leads to a 20% reduction in forced expiratory volume in 1 second [PC20]≤ 16 mg/mL) and those with lower sensitivity (PC 20 > 16 mg/mL). Clinical characteristics were compared between the 2 groups. Results: Among 346 patients, 213 had PC 20 ≤ 16 mg/mL and 133 had PC 20 > 16 mg/mL. The PC20> 16 mg/mL group had a higher prevalence of late-onset asthma (P= 0.024) and obesity (P= 0.045). While no significant differences in immunoglobulin E (≥ 200 IU/mL) were found, the PC 20 ≤ 16 mg/mL group had greater T2-high inflammation, such as elevated eosinophil counts and fractional exhaled nitric oxide (P< 0.001 and P= 0.004, respectively). Asthma exacerbations requiring emergency visits or hospitalizations were more frequent in the PC 20 > 16 mg/mL group, despite a lower proportion of patients on higher-step treatments according to Global Initiative for Asthma guidelines. Conclusion Asthmatic patients with PC 20 > 16 mg/mL tend to present with late-onset asthma, less T2-high inflammation, and higher rates of asthma exacerbations. Further studies are needed to clarify the clinical features of asthma patients with PC 20 > 16 mg/mL and assess the long-term significance of these findings.

Purpose: Methacholine bronchial provocation tests (MBPTs) are commonly used to assess airway hyperresponsiveness, but some patients show no significant response. This study aimed to compare the clinical characteristics of asthmatic patients based on their sensitivity to MBPTs. Methods: We conducted a retrospective cross-sectional study involving adult asthmatic patients from 6 university hospitals in South Korea. Patients were categorized into 2 groups: those with MBPT sensitivity (the provocative concentration of methacholine that leads to a 20% reduction in forced expiratory volume in 1 second [PC20]≤ 16 mg/mL) and those with lower sensitivity (PC 20 > 16 mg/mL). Clinical characteristics were compared between the 2 groups. Results: Among 346 patients, 213 had PC 20 ≤ 16 mg/mL and 133 had PC 20 > 16 mg/mL. The PC20> 16 mg/mL group had a higher prevalence of late-onset asthma (P= 0.024) and obesity (P= 0.045). While no significant differences in immunoglobulin E (≥ 200 IU/mL) were found, the PC 20 ≤ 16 mg/mL group had greater T2-high inflammation, such as elevated eosinophil counts and fractional exhaled nitric oxide (P< 0.001 and P= 0.004, respectively). Asthma exacerbations requiring emergency visits or hospitalizations were more frequent in the PC 20 > 16 mg/mL group, despite a lower proportion of patients on higher-step treatments according to Global Initiative for Asthma guidelines. Conclusion Asthmatic patients with PC 20 > 16 mg/mL tend to present with late-onset asthma, less T2-high inflammation, and higher rates of asthma exacerbations. Further studies are needed to clarify the clinical features of asthma patients with PC 20 > 16 mg/mL and assess the long-term significance of these findings.

Mutations in the Leucine-rich repeat kinase 2 (LRRK2 ) gene are the most prevalent cause of familial Parkinson’s disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S +/- mice. However, a significant increase in ciliogenesis was observed in G2019S +/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.

Background/Aims: Our study aimed to evaluate the long-term outcomes and risk factors forrelapse after anti-tumor necrosis factor (TNF)-α cessation in inflammatory bowel disease (IBD) patients because they are not well established. Methods: A retrospective multicenter cohort study was conducted involving patients with Crohn’s disease (CD) or ulcerative colitis (UC) from 10 referral hospitals in Korea who discontinued firstline anti-TNF therapy after achieving clinical remission. Results: A total of 109 IBD patients (71 CD and 38 UC) with a median follow-up duration of 56months were analyzed. The cumulative relapse rates at 1, 3, and 5 years were 11.3%, 46.7%, and 62.5% for CD patients and 28.9%, 45.3%, and 60.9% for UC patients. Multivariable Coxanalysis revealed that discontinuation owing to the clinician’s decision was associated with lower risk of relapse (vs patient’s preference: hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04 to 0.48; p=0.002) and adalimumab use was associated with higher risk of relapse (vs infliximab: HR, 4.42; 95% CI, 1.24 to 17.74; p=0.022) in CD patients. Mucosal healing was associated with lower risk of relapse (vs nonmucosal healing: HR, 0.12; 95% CI, 0.02 to 0.83; p=0.031) in UC patients. Anti-TNF re-induction was provided to 52 patients, and a response was obtained in 50 patients. However, 25 of them discontinued retreatment owing to a loss of response (n=15), the patient’s preference (n=6), and other factors (n=4). Conclusions More than 60% of IBD patients in remission under anti-TNF therapy relapsed within 5 years of treatment cessation. Anti-TNF re-induction was effective. However, half of the patients discontinued anti-TNF therapy, and 50% of these patients discontinued treatment owing to loss of response.

Background: and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. Methods: This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). Results: Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. Conclusions Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.

Mutations in the Leucine-rich repeat kinase 2 (LRRK2 ) gene are the most prevalent cause of familial Parkinson’s disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S +/- mice. However, a significant increase in ciliogenesis was observed in G2019S +/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.

Background/Aims: Our study aimed to evaluate the long-term outcomes and risk factors forrelapse after anti-tumor necrosis factor (TNF)-α cessation in inflammatory bowel disease (IBD) patients because they are not well established. Methods: A retrospective multicenter cohort study was conducted involving patients with Crohn’s disease (CD) or ulcerative colitis (UC) from 10 referral hospitals in Korea who discontinued firstline anti-TNF therapy after achieving clinical remission. Results: A total of 109 IBD patients (71 CD and 38 UC) with a median follow-up duration of 56months were analyzed. The cumulative relapse rates at 1, 3, and 5 years were 11.3%, 46.7%, and 62.5% for CD patients and 28.9%, 45.3%, and 60.9% for UC patients. Multivariable Coxanalysis revealed that discontinuation owing to the clinician’s decision was associated with lower risk of relapse (vs patient’s preference: hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04 to 0.48; p=0.002) and adalimumab use was associated with higher risk of relapse (vs infliximab: HR, 4.42; 95% CI, 1.24 to 17.74; p=0.022) in CD patients. Mucosal healing was associated with lower risk of relapse (vs nonmucosal healing: HR, 0.12; 95% CI, 0.02 to 0.83; p=0.031) in UC patients. Anti-TNF re-induction was provided to 52 patients, and a response was obtained in 50 patients. However, 25 of them discontinued retreatment owing to a loss of response (n=15), the patient’s preference (n=6), and other factors (n=4). Conclusions More than 60% of IBD patients in remission under anti-TNF therapy relapsed within 5 years of treatment cessation. Anti-TNF re-induction was effective. However, half of the patients discontinued anti-TNF therapy, and 50% of these patients discontinued treatment owing to loss of response.