Background: Neutrophilic inflammation is a characteristic feature of idiopathic pulmonary fibrosis (IPF). S100 calcium-binding protein A9 (S100A9) is a neutrophil-derived protein involved in the development of neutrophil-related chronic inflammatory disorders. However, the role of S100A9 in IPF remains unclear. Methods: We used enzyme-linked immunosorbent assays to measure S100A9 levels in bronchoalveolar lavage fluid (BALF) and serum obtained from healthy controls (HCs) and patients with IPF, non-specific interstitial pneumonia, hypersensitivity pneumonitis, and sarcoidosis. Results: Compared with HCs, BALF S100A9 levels were significantly higher in IPF patients (P < 0.001), patients with hypersensitivity pneumonitis (P = 0.043), and patients with nonspecific interstitial pneumonia (P < 0.001). The S100A9 level in BALF of 0.093 ng/mL could distinguish IPF patients from HCs, with a specificity of 78.8% and a sensitivity of 81.6%. Similarly, the S100A9 level in BALF of 0.239 ng/mL had a specificity of 64.7% and a sensitivity of 66.7% for distinguishing IPF patients from patients with other interstitial lung diseases. Additionally, BALF S100A9 levels were significantly correlated with neutrophil counts (r = 0.356, P < 0.001) in BALF. IPF patients with S100A9 levels in BALF > 0.533 ng/ mL had lower survival rates, compared with patients who had levels ≤ 0.553 ng/mL (n = 49; hazard ratio [HR], 3.62; P = 0.021). Combination analysis revealed that IPF patients with S100A9 levels in BALF> 0.553 ng/mL or neutrophil percentages > 49.1% (n = 43) had significantly lower survival rates than patients with S100A9 levels in BALF ≤ 0.553 ng/mL and neutrophil percentages ≤ 49.1% (n = 41) (HR, 3.91; P = 0.014). Additionally, patients with serum S100A9 levels > 0.077 ng/mL (n = 29) had significantly lower survival rates than patients with levels ≤ 0.077 ng/mL (n = 53, HR, 2.52; P = 0.013). S100A9 was expressed on neutrophils and macrophages in BALF from IPF patients as well as α-smooth muscle actin positive cells in the lung tissues. Conclusion S100A9 is involved in the development and progression of IPF. Moreover, S100A9 levels in BALF and serum may be surrogate markers for IPF diagnosis and survival prediction, particularly when analyzed in combination with neutrophil percentages.

Purpose: There are few reports on outcomes following surgical repair of recurrent rectal prolapse. The purpose of this study was to examine surgical outcomes for recurrent rectal prolapse. Methods: We conducted a multicenter retrospective study of patients who underwent surgery for recurrent rectal prolapse. This study used data collected by the Korean Anorectal Physiology and Pelvic Floor Disorder Study Group. Results: A total of 166 patients who underwent surgery for recurrent rectal prolapse were registered retrospectively between 2011 and 2016 in 8 referral hospitals. Among them, 153 patients were finally enrolled, excluding 13 patients who were not followed up postoperatively. Median follow-up duration was 40 months (range, 0.2–129.3 months). Methods of surgical repair for recurrent rectal prolapse included perineal approach (n = 96) and abdominal approach (n = 57). Postoperative complications occurred in 16 patients (10.5%). There was no significant difference in complication rate between perineal and abdominal approach groups. While patients who underwent the perineal approach were older and more fragile, patients who underwent the abdominal approach had longer operation time and admission days (P < 0.05). Overall, 29 patients (19.0%) showed re-recurrence after surgery. Among variables, none affected the re-recurrence. Conclusion For the recurrent rectal prolapse, the perineal approach is used for the old and fragile patients. The postoperative complications and re-recurrence rate between perineal and abdominal approach were not different significantly. No factor including surgical method affected re-recurrence for recurrent rectal prolapse.

Background/Aims: Neutrophilia is frequently observed in bronchoalveolar lavage fluid (BALF) of idiopathic pulmonary fibrosis (IPF) patients. Granulocyte colony-stimulating factor (G-CSF) is a potent neutrophil-activating glycoprotein. However, the clinical implications of G-CSF remain poorly understood.in patients with IPF. Therefore, we evaluated the relationship between the G-CSF concentration in BALF and the progression of fibrosis, including in terms of the decline in lung function and long-term survival rate. Methods: G-CSF concentrations were measured in BALF using enzyme-linked immunosorbent assay (ELISA). The survival rate was estimated using Kaplan-Meier survival analyses. Results: G-CSF protein levels were significantly higher in IPF (n = 87; 1.88 [0 to 5.68 pg/mL]), nonspecific interstitial pneumonia (n = 22; 0.58 [0 to 11.64 pg/mL]), and hypersensitivity pneumonitis (n = 19; 2.48 [0.46 to 5.71 pg/mL]) patients than in normal controls (n = 33; 0 [0 to 0.68 pg/mL]) (all p < 0.01). A receiver operating characteristic curve showed a difference in G-CSF levels between IPF and NC (area under the curve, 0.769): The G-CSF cut-off of 0.96 pg/mL indicated 84.9% specificity and 63.2% sensitivity for IPF. The survival rate was significantly lower in the group with G-CSF > 2.872 pg/mL than in the group with ≤ 2.872 pg/mL (hazard ratio, 2.69; p = 0.041). The annual decline in diffusing capacity of the lung for carbon monoxide was positively correlated with the G-CSF level (p = 0.018). Conclusions G-CSF may participate in the development of IPF and be useful for predicting the prognosis of IPF. Therefore, G-CSF should be analyzed in BALF, in addition to differential cell counts.

Background/Aims: Coronavirus disease 2019 (COVID-19) is associated with acute respiratory syndrome. The mechanisms underlying the different degrees of pneumonia severity in patients with COVID-19 remain elusive. This study provides evidence that COVID-19 is associated with eosinophil-mediated inflammation. Methods: We performed a retrospective case series of three patients with laboratory and radiologically confirmed COVID-19 pneumonia admitted to Chosun University Hospital. Demographic and clinical data on inflammatory cell lung infiltration and cytokine levels in patients with COVID-19 were collected. Results: Cytological analysis of sputum, tracheal aspirates, and bronchoalveolar lavage fluid (BALF) samples from all three patients revealed massive infiltration of polymorphonuclear cells (PMNs), such as eosinophils and neutrophils. All sputum and BALF specimens contained high levels of eosinophil cationic proteins. The infiltration of PMNs into the lungs, together with elevated levels of natural killer T (NKT) cells in BALF and peripheral blood samples from patients with severe pneumonia in the acute phase was confirmed by flow cytometry. Conclusions These results suggest that the lungs of COVID-19 patients can exhibit eosinophil-mediated inflammation, together with an elevated NKT cell response, which is associated with COVID-19 pneumonia.

Background/Aims: The efficacy and safety of mepolizumab in patients with severe eosinophilic asthma has been evaluated in a global clinical trial programme. This post hoc analysis assesses the efficacy and safety of mepolizumab in Korean patients. Methods: Data from Korean patients in the Phase III, placebo-controlled, randomised DREAM (MEA112997/NCT01000506) and MENSA (MEA115588/ NCT01691521) studies were included. Patients ≥ 12 years old with severe eosinophilic asthma received mepolizumab (DREAM: 75, 250 or 750 mg intravenously [IV]; MENSA: 75 mg IV or 100 mg subcutaneously [SC]), or placebo every 4 weeks for 52 weeks (DREAM) or 32 weeks (MENSA). The primary outcome was the rate of clinically significant asthma exacerbations. Secondary outcomes included forced expiratory volume in 1 second (FEV1), Asthma Control Questionnaire (ACQ) and St George’s Respiratory Questionnaire (SGRQ) scores (MENSA only). Blood eosinophil counts (BEC) and safety were assessed throughout. Results: Reductions in the rate of clinically significant asthma exacerbations were observed with the approved (100 mg SC) and bioequivalent (75 mg IV) doses of mepolizumab in Korean patients who participated in DREAM and MENSA. In MENSA, trends for improvements from baseline at week 32 in pre-bronchodilator FEV1 (75 mg IV group), ACQ-5 and SGRQ scores (in both treatment groups) were seen versus placebo in Korean patients. Incidence of on-treatment adverse events was similar in Korean patients versus non-Korean patients as were observed reductions from baseline in BEC. Conclusions Mepolizumab treatment provided clinical benefits for Korean patients with severe eosinophilic asthma; the safety profile is consistent with the overall population.

Background/Aims: Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. Methods: This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. Results: Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). Conclusions Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.

Background/Aims: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a major regulator of Wnt signaling, which is involved in fibroblast dysfunction. Because its role has not been evaluated in idiopathic pulmonary fibrosis (IPF), we examined the clinical implications of ROR2 expression. Methods: ROR2 mRNA expression was measured using reverse transcription polymerase chain reaction in lung tissue-derived fibroblasts from IPF patients (n = 14) and from controls (n = 10). ROR2 protein was measured using enzyme-linked immunosorbent assay in primary fibroblasts from IPF patients (n = 14) and controls (n = 10), and in bronchoalveolar lavage (BAL) fluids obtained from normal controls (NC; n = 30). IPF patients (n = 84), and other patients with interstitial lung diseases, including nonspecific interstitial pneumonia (NSIP; n = 10), hypersensitivity pneumonitis (HP; n = 10), and sarcoidosis (n = 10). Results: ROR2 mRNA and protein levels were significantly higher in IPF fibroblasts than in controls (p = 0.003, p = 0.0017, respectively). ROR2 protein levels in BAL fluids from patients with IPF were significantly higher than in those from NC (p < 0.001), and from patients with NSIP (p = 0.006), HP (p = 0.004), or sarcoidosis (p = 0.004). Receiver operating characteristic curves showed a clear difference between IPF and NC in ROR2 protein level (area under the curve, 0.890; confidence interval, 0.829 to 0.950; p < 0.001). ROR2 protein levels were significantly higher in GAP stage III than in GAP stages I and II (p = 0.016). Conclusions ROR2 may be related to the development of IPF, and its protein level may be a useful and severity-dependent candidate marker for IPF.

Background/Aims: Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. Methods: This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. Results: Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). Conclusions Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.

Background/Aims: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a major regulator of Wnt signaling, which is involved in fibroblast dysfunction. Because its role has not been evaluated in idiopathic pulmonary fibrosis (IPF), we examined the clinical implications of ROR2 expression. Methods: ROR2 mRNA expression was measured using reverse transcription polymerase chain reaction in lung tissue-derived fibroblasts from IPF patients (n = 14) and from controls (n = 10). ROR2 protein was measured using enzyme-linked immunosorbent assay in primary fibroblasts from IPF patients (n = 14) and controls (n = 10), and in bronchoalveolar lavage (BAL) fluids obtained from normal controls (NC; n = 30). IPF patients (n = 84), and other patients with interstitial lung diseases, including nonspecific interstitial pneumonia (NSIP; n = 10), hypersensitivity pneumonitis (HP; n = 10), and sarcoidosis (n = 10). Results: ROR2 mRNA and protein levels were significantly higher in IPF fibroblasts than in controls (p = 0.003, p = 0.0017, respectively). ROR2 protein levels in BAL fluids from patients with IPF were significantly higher than in those from NC (p < 0.001), and from patients with NSIP (p = 0.006), HP (p = 0.004), or sarcoidosis (p = 0.004). Receiver operating characteristic curves showed a clear difference between IPF and NC in ROR2 protein level (area under the curve, 0.890; confidence interval, 0.829 to 0.950; p < 0.001). ROR2 protein levels were significantly higher in GAP stage III than in GAP stages I and II (p = 0.016). Conclusions ROR2 may be related to the development of IPF, and its protein level may be a useful and severity-dependent candidate marker for IPF.