Factors Associated with Postoperative Recurrence in Stage I to IIIA Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data.

Purpose: Recent development in perioperative treatment of resectable non-small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion: Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Progression to ANCA-associated vasculitis in patients with idiopathic interstitial pneumonia and positive ANCA.

OBJECTIVE: This study explored the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its risk factors in patients with idiopathic interstitial pneumonia (IIP) and positive ANCA results. METHODS: Data of patients diagnosed with IIP with positive ANCA results at a single tertiary center in South Korea were retrospectively reviewed from January 2013 to August 2023. Cox regression analysis was performed to identify variables associated with AAV occurrence following IIP diagnosis. Kaplan-Meier curves were employed to investigate the relationship between autoantibodies and the occurrence of AAV. RESULTS: In a cohort of 154 IIP-diagnosed patients with positive ANCA results but without AAV, 10.4 % of them eventually developed AAV. The AAV and non-AAV groups did not significantly differ by sex, age, smoking status, urinalysis, or chest computed tomography findings. All the patients who subsequently developed AAV were anti-myeloperoxidase (MPO) positive, while 48.8 % of the non-AAV patients were anti-MPO positive (P < 0.001). Rheumatoid factor (RF) positivity differed significantly (62.5 % vs. 29.2 %, P = 0.007) between the AAV and non-AAV groups. Multivariate Cox regression and Kaplan-Meier analyses revealed RF (HR 4.02; P = 0.004) and anti-MPO (HR 38.10; P < 0.001) positivity as risk factors associated with AAV occurrence. CONCLUSION: Approximately 10 % of ANCA-positive IIP patients developed AAV after an IIP diagnosis. Anti-MPO or co-occurring positive RF poses a significant risk for subsequent AAV occurrence. This emphasizes the importance of careful monitoring in patients with high-risk antibody profiles, even if the complete features of AAV are not present at IIP diagnosis.

Added value of 40 keV virtual monoenergetic images for diagnosing malignant pleural effusion on chest CT.

OBJECTIVE: This study aimed to evaluate the added value of 40 keV virtual mono-energetic images (VMIs) obtained from dual-layer detector CT (DLCT) for diagnosing malignant pleural effusion (MPE) in patients presenting with unilateral pleural effusion on chest CT. MATERIALS AND METHODS: This retrospective study included 75 patients with unilateral pleural effusion who underwent contrast-enhanced chest CT scans using DLCT. Quantitative and qualitative assessments of the visibility of pleural thickening were conducted on both conventional 120 kVp images and 40 keV VMIs. Two independent radiologists reviewed chest CT scans with or without 40 keV VMIs to detect pleural nodules or nodular thickening for the diagnosis of MPE. Diagnostic performances were compared and independent predictors of MPE were identified through multivariate logistic regression analysis using CT and clinicopathologic findings. RESULTS: Pleural thickening associated with MPE demonstrated a higher contrast-to-noise ratio value and greater visual conspicuity in 40 keV VMIs compared to benign effusions (p < 0.05). For both readers, the use of 40 keV VMIs significantly improved (p < 0.05) the diagnostic performance in terms of sensitivity and area under the curve (AUC) for diagnosing MPE through the detection of pleural nodularity. Inter-observer agreements between the two readers were substantial for both 120 kVp images alone and the combined use of 40 keV VMIs. Initial cytology results and pleural nodularity at 40 keV were identified as independent predictors of MPE. CONCLUSION: The use of 40 keV VMIs from DLCT can improve diagnostic performance of readers in detecting MPE among patients with unilateral pleural effusion.

Clinical characteristics and outcome of lung cancer in patients with fibrosing interstitial lung disease.

BACKGROUND: Lung cancer (LC) is an important comorbidity of interstitial lung disease (ILD) and has a poor prognosis. The clinical characteristics and outcome of each ILD subtype in LC patients have not been sufficiently investigated. Therefore, this study aimed to evaluate the difference between idiopathic pulmonary fibrosis (IPF) and non-IPF ILD as well as prognostic factors in patients with ILD-LC. METHODS: The medical records of 163 patients diagnosed with ILD-LC at Asan Medical Center from January 2018 to May 2023 were retrospectively reviewed. Baseline characteristics and clinical outcomes were compared between the IPF-LC and non-IPF ILD-LC groups, and prognostic factors were analyzed using the Cox proportional-hazard model. RESULTS: The median follow-up period was 11 months after the cancer diagnosis. No statistically significant differences were observed in clinical characteristics and mortality rates (median survival: 26 vs. 20 months, p = 0.530) between the groups. The independent prognostic factors in patients with ILD-LC were higher level of Krebs von den Lungen-6 (≥ 1000 U/mL, hazard ratio [HR] 1.970, 95% confidence interval [CI] 1.026-3.783, p = 0.025) and advanced clinical stage of LC (compared with stage I, HR 3.876 for stage II, p = 0.025, HR 5.092 for stage III, p = 0.002, and HR 5.626 for stage IV, p = 0.002). In terms of treatment, surgery was the significant factor for survival (HR 0.235; 95% CI 0.106-0.520; p < 0.001). CONCLUSIONS: No survival difference was observed between IPF-LC and non-IPF ILD-LC patients. A higher level of Krebs von den Lungen-6 may act as a prognostic marker in ILD-LC patients.

Factors Associated with the Discrepancy between Exercise Capacity and Airflow Limitation in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Exercise capacity is associated with lung function decline in chronic obstructive pulmonary disease (COPD) patients, but a discrepancy between exercise capacity and airflow limitation exists. This study aimed to explore factors contributing to this discrepancy in COPD patients. METHODS: Data for this prospective study were obtained from the Korean COPD Subgroup Study. The exercise capacity and airflow limitation were assessed using the 6-minute walk distance (6-MWD; m) and forced expiratory volume in 1 second (FEV1). Participants were divided into four groups: FEV1 >50%+6-MWD >350, FEV1 >50%+6- MWD ≤350, FEV1 ≤50%+6-MWD >350, and FEV1 ≤50%+6-MWD ≤350 and their clinical characteristics were compared. RESULTS: A total of 883 patients (male:female, 822:61; mean age, 68.3±7.97 years) were enrolled. Among 591 patients with FEV1 >50%, 242 were in the 6-MWD ≤350 group, and among 292 patients with FEV1 ≤50%, 185 were in the 6-MWD >350 group. The multiple regression analyses revealed that male sex (odds ratio [OR], 8.779; 95% confidence interval [CI], 1.539 to 50.087; p=0.014), current smoking status (OR, 0.355; 95% CI, 0.178 to 0.709; p=0.003), and hemoglobin levels (OR, 1.332; 95% CI, 1.077 to 1.648; p=0.008) were significantly associated with discrepancies in exercise capacity and airflow limitation in patients with FEV1 >50%. Meanwhile, in patients with FEV1 ≤50%, diffusion capacity of carbon monoxide (OR, 0.945; 95% CI, 0.912 to 0.979; p=0.002) was significantly associated with discrepancies between exercise capacity and airflow limitation. CONCLUSION: The exercise capacity of COPD patients may be influenced by factors other than airflow limitation, so these aspects should be considered when assessing and treating patients.

Population pharmacokinetic model of rifampicin for personalized tuberculosis pharmacotherapy: Effects of SLCO1B1 polymorphisms on drug exposure.

BACKGROUND: Rifampicin (RIF) exhibits high pharmacokinetic (PK) variability among individuals; a low plasma concentration might result in unfavorable treatment outcomes and drug resistance. This study evaluated the contributions of non- and genetic factors to the interindividual variability of RIF exposure, then suggested initial doses for patients with different weight bands. METHODS: This multicenter prospective cohort study in Korea analyzed demographic and clinical data, the solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotypes, and RIF concentrations. Population PK modeling and simulations were conducted using nonlinear mixed-effect modeling. RESULTS: In total, 879 tuberculosis (TB) patients were divided into a training dataset (510 patients) and a test dataset (359 patients). A one-compartment model with allometric scaling for effect of body size best described the RIF PKs. The apparent clearance (CL/F) was 16.6% higher among patients in the SLCO1B1 rs4149056 wild-type group than among patients in variant group, significantly decreasing RIF exposure in the wild-type group. The developed model showed better predictive performance compared with previously reported models. We also suggested that patients with body weights of <40 kg, 40-55 kg, 55-70 kg, and >70 kg patients receive RIF doses of 450, 600, 750, and 1050 mg/day, respectively. CONCLUSIONS: Total body weight and SLCO1B1 rs4149056 genotypes were the most significant covariates that affected RIF CL/F variability in Korean TB patients. We suggest initial doses of RIF based on World Health Organization weight-band classifications. The model may be implemented in treatment monitoring for TB patients.

Clinical characteristics and prognostic impact of acute exacerbations in patients with interstitial lung disease and lung cancer: A single-center, retrospective cohort study.

BACKGROUND: Although acute exacerbation (AE) after treatment for lung cancer (LC) is a poor prognostic factor in patients with interstitial lung disease associated with lung cancer (ILD-LC), the risk of AE according to cancer treatment type remains unclear. Therefore, in the present study, we aimed to investigate the association between AE and treatment received for LC in patients with ILD-LC. METHODS: We conducted a retrospective study of patients with ILD-LC who had undergone treatment for LC between January 2018 and December 2022. The primary study outcome was the incidence of AE within 12 months of treatment for LC according to treatment type. The association between AE and all-cause mortality was evaluated as a secondary outcome. RESULTS: Among a total of 137 patients, 23 (16.8%) developed AE within 12 months of treatment for LC. The incidence of AE according to treatment type was 4.3% for surgery, 16.2% for radiotherapy, 15.6% for chemotherapy, and 54.5% for concurrent chemoradiation therapy (CCRT). Patients who received CCRT were more likely to develop AE, even after adjustment for covariables (hazard ratio [HR], 15.39; 95% confidence interval [CI]: 4.00-59.19; p < 0.001). In addition, AE within 12 months of treatment for LC was associated with an increased risk of all-cause mortality (HR, 2.82; 95% CI: 1.13-7.04; p = 0.026). CONCLUSION: Among treatment options for patients with ILD-LC, CCRT was associated with an increased risk for AE. In addition, patients with AE had a higher mortality rate than patients without AE.

Early Gait Function After Lung Transplantation in Patients With and Without Pretransplant Extracorporeal Membrane Oxygenation Support.

OBJECTIVE: We aimed to investigate the recovery of gait function, muscle strength, and the achievement of an independent gait after lung transplantation (LT) in patients with and without pretransplant extracorporeal membrane oxygenation (ECMO) support. METHODS: We retrospectively reviewed the medical records of 33 inpatients who underwent bilateral LT and received physical therapy. We assessed the Functional Ambulatory Category (FAC) and Manual Muscle Test (MMT) scores at baseline, 1 month, and 3 months of rehabilitation and the time it took to achieve a FAC score of 3 within 3 months of LT surgery in ECMO and non-ECMO patients. RESULTS: The FAC and MMT scores were generally improved during the first 3 months after LT. The number of patients who achieved a FAC score of 3 at 3 months did not significantly differ between the ECMO and non-ECMO groups (P = .193). At 1 month, significantly fewer patients had reached a FAC of 3 in the ECMO group than in the non-ECMO group (P = .042). There were no significant differences in the FAC (P = .398) and MMT scores (P = .079) at 3 months between the 2 groups. CONCLUSIONS: Both groups' gait function and muscle strength were continuously restored 3 months after LT. At 1 month, the gait function was assessed by the FAC score, and the rate to achieve a FAC of 3 was higher in the non-ECMO group than in the ECMO group, but at 3 months, the difference was not significant between the 2 groups.

Clinical impact of weight loss on mortality in patients with idiopathic pulmonary fibrosis: a retrospective cohort study.

Patients with idiopathic pulmonary fibrosis (IPF) often experience weight loss during the follow-up period. However, the prevalence and clinical impact of weight loss in these patients still need to be elucidated. This retrospective single-center study reviewed 134 consecutive patients diagnosed with IPF. Weight loss of 5% or more over 1 year was defined as significant weight loss. Clinical data of patients were compared according to the significant weight loss. We analyzed whether the clinical impact of significant weight loss differed regarding the pirfenidone dose. The median follow-up period was 22.1 months. The mean age of patients was 67.3 years, and 92.5% were men. Of the 134 patients, 42 (31.3%) showed significant weight loss. Multivariate cox regression analysis revealed that significant weight loss was independently associated with mortality (hazard ratio [HR]; 2.670; 95% confidence interval [CI] 1.099-6.484; p = 0.030) after adjusting for lung function and other significant risk factors (6-min walk test distance: HR, 0.993; 95% CI 0.987-0.998; p = 0.005). The median survival of patients with significant weight loss (n = 22) was relevantly shorter than that of those without significant weight loss (n = 43) in the reduced dose pirfenidone group (28.2 ± 3.3 vs. 43.3 ± 3.2 months, p = 0.013). Compared with patients without significant weight loss (n = 38), patients with significant weight loss (n = 15) also showed a marginally-significant shorter survival in the full-dose pirfenidone group (28.9 ± 3.1 vs. 39.8 ± 2.6 months, p = 0.085). Significant weight loss is a prognostic factor in patients with IPF regardless of pirfenidone dose. Vigilant monitoring might be necessary to detect weight loss during the clinical course in these patients.

Epidemiology and comorbidities in idiopathic pulmonary fibrosis: a nationwide cohort study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is frequently accompanied by comorbidities, with the management of these comorbidities crucial for clinical outcomes. This study investigated the prevalence, incidence, changes over time, and clinical impact of comorbidities in IPF patients, based on nationwide claims data in South Korea. METHODS: This retrospective cohort study utilised nationwide health claim data in South Korea between 2011 and 2019. Patients with IPF were defined as those with ICD-10 code J84.1 and Rare Intractable Disease code V236 who made at least one claim per year. Patients were classified by sex, age, pirfenidone use and burden of comorbidities, and differences among groups were determined. RESULTS: The yearly prevalence rate of IPF increased from 7.50 to 23.20 per 100,000 people, and the yearly incidence rate increased from 3.56 to 7.91 per 100,000 person-years over time. The most common respiratory comorbidity was chronic obstructive pulmonary disease (37.34%), followed by lung cancer (3.34%), whereas the most common non-respiratory comorbidities were gastro-oesophageal reflux disease (70.83%), dyslipidaemia (62.93%) and hypertension (59.04%). The proportion of some comorbidities differed by sex, age and use of pirfenidone. The proportion of lung cancer was higher in patients treated with pirfenidone, whereas the proportion of anxiety and depression were lower in patients not treated with pirfenidone. Charlson comorbidity index ≥ 4 was associated with increases in hospitalisations and total medical costs. CONCLUSIONS: The yearly prevalence and incidence of IPF and comorbidities in Korea increased over time. These comorbidities affected the use of pirfenidone and medical resources.

Factors associated with dose reduction of pirfenidone in patients with idiopathic pulmonary fibrosis: A study based on real-world clinical data.

INTRODUCTION: Although pirfenidone slows disease progression in patients with idiopathic pulmonary fibrosis (IPF), in clinical practice, patients often cannot tolerate the recommended dose because of several adverse events. This study aimed to investigate adverse events associated with pirfenidone and factors associated with dose reduction. METHODS: This single-center retrospective cohort study included 156 consecutive patients with IPF who received pirfenidone. Demographic characteristics, pulmonary function, and pirfenidone-related adverse events were investigated. We compared patients who received standard and reduced doses of pirfenidone. RESULTS: The mean patient age was 69.7 years. The median follow-up duration was 243 days. The low-dose group (n = 73) included older patients (71.0 years vs. 67.4 years, p = 0.016), fewer smokers (80.8% vs. 96.4%, p = 0.008), and patients with a lower body mass index (BMI; 24.1 kg/m2 vs. 25.7 kg/m2, p = 0.027) than the standard dose group (n = 57). Multivariate logistic regression analysis revealed that older age (odds ratio = 1.066, p = 0.016) was significantly associated with dose reduction of pirfenidone after adjusting for sex, smoking history, emphysema, and BMI. No significant difference was found in the rates of a reduced forced vital capacity and diffusing capacity for carbon monoxide between the two groups. CONCLUSIONS: Although older patients are more likely to undergo dose reduction of pirfenidone, low-dose pirfenidone might be effective for treating patients with IPF. Low-dose pirfenidone could be considered an effective treatment option for older patients with IPF.

Venous thromboembolism in patients with idiopathic pulmonary fibrosis, based on nationwide claim data.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a known risk factor for venous thromboembolism (VTE). However, it is currently unknown which factors are associated with an increase of VTE in patients with IPF. OBJECTIVES: We estimated the incidence of VTE in patients with IPF and identified clinical characteristics related to VTE in patients with IPF. DESIGN AND METHODS: De-identified nationwide health claim data from 2011 to 2019 was collected from the Korean Health Insurance Review and Assessment database. Patients with IPF were selected if they had made at least one claim per year under the J84.1 [International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10)] and V236 codes of rare intractable diseases. We defined the presence of VTE as at least one claim of pulmonary embolism and deep vein thrombosis ICD-10 codes. RESULTS: The incidence rate per 1000 person-years of VTE was 7.08 (6.44-7.77). Peak incidence rates were noted in the 50-59 years old male and 70-79 years old female groups. Ischemic heart disease, ischemic stroke, and malignancy were associated with VTE in patients with IPF, with an adjusted hazard ratio (aHR) of 1.25 (1.01-1.55), 1.36 (1.04-1.79), and 1.53 (1.17-2.01). The risk for VTE was increased in patients diagnosed with malignancy after IPF diagnosis (aHR = 3.18, 2.47-4.11), especially lung cancer [hazard ratio (HR) = 3.78, 2.90-4.96]. Accompanied VTE was related to more utilization of medical resources. CONCLUSION: Ischemic heart disease, ischemic stroke, and malignancy, especially lung cancer, were related to higher HR for VTE in IPF.

Five-Year Overall Survival and Prognostic Factors in Patients with Lung Cancer: Results from the Korean Association of Lung Cancer Registry (KALC-R) 2015.

PURPOSE: This study aimed to provide the clinical characteristics, prognostic factors, and 5-year relative survival rates of lung cancer diagnosed in 2015. MATERIALS AND METHODS: The demographic risk factors of lung cancer were calculated using the KALC-R (Korean Association of Lung Cancer Registry) cohort in 2015, with survival follow-up until December 31, 2020. The 5-year relative survival rates were estimated using Ederer II methods, and the general population data used the death rate adjusted for sex and age published by the Korea Statistical Information Service from 2015 to 2020. RESULTS: We enrolled 2,657 patients with lung cancer who were diagnosed in South Korea in 2015. Of all patients, 2,098 (79.0%) were diagnosed with non-small cell lung cancer (NSCLC) and 345 (13.0%) were diagnosed with small cell lung cancer (SCLC), respectively. Old age, poor performance status, and advanced clinical stage were independent risk factors for both NSCLC and SCLC. In addition, the 5-year relative survival rate declined with advanced stage in both NSCLC (82%, 59%, 16%, 10% as the stage progressed) and SCLC (16%, 4% as the stage progressed). In patients with stage IV adenocarcinoma, the 5-year relative survival rate was higher in the presence of epidermal growth factor receptor (EGFR) mutation (19% vs. 11%) or anaplastic lymphoma kinase (ALK) translocation (38% vs. 11%). CONCLUSION: In this Korean nationwide survey, the 5-year relative survival rates of NSCLC were 82% at stage I, 59% at stage II, 16% at stage III, and 10% at stage IV, and the 5-year relative survival rates of SCLC were 16% in cases with limited disease, and 4% in cases with extensive disease.

Enfortumab vedotin-related pneumonitis is more common than expected and could lead to acute respiratory failure.

PURPOSE: To analyse the incidence of pneumonitis related to enfortumab vedotin (EV) in patients with metastatic urothelial cell carcinoma (mUC). METHODS: Patients with mUC who participated in two EV clinical trials in South Korea were analysed for the incidence and clinical course of EV-related pneumonitis through retrospective, independent review. The clinical characteristics and radiologic attributes of potential pneumonitis were identified and reviewed by the participating investigators and pulmonologists. RESULTS: Between October 2018 and January 2020, 64 patients were enrolled in the EV-201 and EV-301 trials across eight institutions in South Korea and were treated with EV. Among them, 18 (28.1%) developed all-grade EV-related pneumonitis, from which 2 (11.1%) patients died. The median time between the last dosing of immunotherapy and the start of EV was 5.6 weeks (range, 0.71-143.1). The median time from the start of EV treatment to the onset of pneumonitis was 13 weeks (range, 2.7-51.0). Of the patients who developed pneumonitis, 7 (38.9%) were clinically asymptomatic. The most common radiologic finding was organising pneumonia (66.7%). CONCLUSIONS: Although we could not rule out the relationship with prior immunotherapy administration, EV-related pneumonitis occurred in approximately 25% of the patients who had received EV in two prospective clinical trials, from which two died. Clinicians should closely monitor patients who have experienced immunotherapy treatment failure for the development of pneumonitis. A delay between initiating EV after termination of immunotherapy should be considered with caution.

Sex differences in the characteristics and survival of patients with non-small-cell lung cancer: A retrospective analytical study based on real-world clinical data of the Korean population.

PURPOSE: This study aimed to investigate the differences in characteristics, clinical stages, treatment modalities, and survival outcomes in patients with non-small-cell lung cancer (NSCLC) based on sex differences using Korean nationwide registry data. METHODS: We analyzed the data of 8650 patients diagnosed with NSCLC between 2014 and 2017, obtained from the Korean Association for Lung Cancer Registry (KALC-R). The Cox proportional hazard model was used to define the differences in survival based on sex. Propensity score matching was used to adjust for differences between men and women. RESULTS: Of a total of 10 943 patients, 8650 (79.1%) were diagnosed with NSCLC, of whom 68.7% were men and 31.3% were women. For NSCLC, the median age was higher (69.0 vs. 67.0, p < 0.001) and the proportion of ever-smokers (84.5% vs. 10.8%, p < 0.001) was higher in men. Adenocarcinoma (55.5% vs. 90.4%, p < 0.001) and stage I NSCLC (26.3% vs. 41.3%, p < 0.001) were more common in women. Survival was significantly lower in men with NSCLC (hazard ratio [HR] 1.493 [95% confidence interval, CI 1.238-1.800], p < 0.001) even after adjusting for meaningful clinical variables, and in the matched cohort (HR 1.339 [1.075-1.667], p = 0.009). Similarly, survival was significantly lower in men with stage IV adenocarcinoma after adjusting for other clinical variables (HR 1.493 [1.238-1.800], p < 0.001) and in the matched cohort (HR 1.339 [1.075-1.667]; p = 0.009). CONCLUSIONS: Male patients with NSCLC had poorer prognosis, not only after variable adjustments for prognostic factors, but also in the matched cohort.

Epidemiology and clinical features of Birt-Hogg-Dubé syndrome: A nationwide population-based study in South Korea.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is an ultrarare lung disease with unclear prevalence and incidence. Our study aimed to identify the epidemiological and clinical features of BHD syndrome by using nationwide claims data from the Korean Health Insurance Review and Assessment service. METHODS: Patients with BHD syndrome who had the following criteria were included: 1) tested for folliculin gene mutation, and 2) had at least one of the conditions: other specified malformation syndromes, fibrofolliculoma, acrochordon, lung cyst, cancer, and pneumothorax based on International Classification of Disease-10 code. RESULTS: We found 26 patients with BHD syndrome from 2017 to 2019. The prevalence of BHD syndrome was 5.67 per 107 population, with no peak age. Among incidence cases, the median age of diagnosis was 51 years, with slightly more females than males (n = 15, 57.7%). Over half of the patients (n = 14, 53.8%) experienced pneumothorax, and 10 (38.5%) developed malignant neoplasm within the clinical course. CONCLUSIONS: The prevalence of BHD syndrome in Korea is extremely low. However, affected patients manifest several comorbidities, including malignant neoplasm and repetitive pneumothorax.

Baseline serum Krebs von den Lungen-6 as a biomarker for the disease progression in idiopathic pulmonary fibrosis.

Disease progression (DP) is an important parameter for the prognosis of idiopathic pulmonary fibrosis (IPF). This study aimed to evaluate the baseline serum biomarkers for predicting the DP in IPF. Seventy-four patients who were diagnosed with IPF and had their serum Krebs von den Lungen-6 (KL-6) and monocyte count, which might be associated with prognosis of IPF, checked more than twice were included. KL-6 ≥ 1000 U/mL and monocyte ≥ 600/µL were arbitrarily set as the cut-off values for DP. The DP was defined as a 10% reduction in forced vital capacity, a 15% reduction in diffusing capacity of the lung for carbon monoxide relative to the baseline, or disease-related mortality. Of the 74 patients, 18 (24.3%) were defined as having DP. The baseline KL-6 level was significantly increased in the DP group compared to the stable disease group (median, 1228.0 U/mL vs. 605.5 U/mL, P = 0.019). Multivariate Cox analyses demonstrated that a high KL-6 level (KL-6 ≥ 1000 U/mL; hazard ratio, 2.761 or 2.845; P = 0.040 or 0.045) was independently associated with DP in each model. The baseline serum KL-6 level might be a useful biomarker for DP in IPF.

Impact of coexistent preserved ratio impaired spirometry on the survival of patients with lung cancer: Analysis of data from the Korean Association for Lung Cancer Registry.

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is a common spirometric pattern that is associated with respiratory symptoms and higher mortality rates. However, the relationship between lung cancer and PRISm remains unclear. This study investigated the clinical characteristics of lung cancer patients with PRISm and the potential role of PRISm as a prognostic factor. METHODS: We retrospectively reviewed data collected from 2014 to 2015 in the Korean Association for Lung Cancer Registry. We classified all patients into three subgroups according to lung function as follows: normal lung function; PRISm (forced expiratory volume in 1 s [FEV1 ] < 80% predicted and FEV1 /forced vital capacity [FVC] ≥ 0.7); and chronic obstructive pulmonary disease (COPD; FEV1/FVC < 0.7). In non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the overall survival period was compared among the three subgroups. The prognostic factors were investigated using Cox regression analysis. RESULTS: Of the 3763 patients, 38.6%, 40.1%, and 21.3% had normal lung function, COPD, and PRISm, respectively. Patients with PRISm had poorer overall survival than those with COPD or normal lung function in NSCLC and SCLC (Mantel-Cox log-rank test, p < 0.05). In the risk-adjusted analysis, overall survival was independently associated with COPD (hazard ratio [HR] 1.209, p = 0.027) and PRISm (HR 1.628, p < 0.001) in NSCLC, but was only associated with PRISm (HR 1.629, p = 0.004) in SCLC. CONCLUSIONS: PRISm is a significant pattern of lung function in patients with lung cancer. At the time of lung cancer diagnosis, pre-existing PRISm should be considered a predictive factor of poor prognosis.

Serum hepatocyte growth factor as a predictor of disease severity and future exacerbations in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: Serum biomarkers associated with the severity of non-cystic fibrosis (CF) bronchiectasis are insufficient. This study determined the association of serum hepatocyte growth factor (HGF), osteopontin, and pentraxin-3 levels with disease severity and exacerbation in patients with non-CF bronchiectasis. METHODS: Serum levels of HGF, osteopontin, and pentraxin-3 were measured in patients with clinically stable non-CF bronchiectasis (n = 61). The correlation between the biomarkers and bronchiectasis severity index (BSI) and FACED score was assessed using univariate and multivariate linear regression analyses. Predictive variables associated with exacerbation were analyzed using a Cox proportional hazards model and the time to first exacerbation in high and low HGF groups during the observation period was compared using Kaplan-Meier survival curves. RESULTS: The BSI showed significant correlation with HGF (r = 0.423; p = 0.001) and pentraxin-3 (r = 0.316; p = 0.013). The FACED score was significantly correlated with HGF (r = 0.406; p = 0.001). Univariate and multivariate linear regression analysis revealed that serum level of HGF was independently associated with both scoring systems. The high HGF group showed a significantly shorter time to first exacerbation (Log-rank test, p = 0.014). Multivariate Cox proportional hazards regression analysis revealed that high serum HGF level and colonization with non-pseudomonas organisms were independent predictors of future exacerbations (HR 2.364; p = 0.024 and HR 2.438; p = 0.020, respectively). CONCLUSION: Serum level of HGF is a potential biomarker that is closely associated with disease severity and future risk of exacerbations in patients with non-CF bronchiectasis.

Development of Brain Metastases in Patients With Non-Small Cell Lung Cancer and No Brain Metastases at Initial Staging Evaluation: Cumulative Incidence and Risk Factor Analysis.

BACKGROUND. Although established guidelines give indications for performing staging brain MRI at initial diagnosis of non-small cell lung cancer (NSCLC), guidelines are lacking for performing surveillance brain MRI for patients without brain metastases at presentation. OBJECTIVE. The purpose of this study is to estimate the cumulative incidence of and risk factors for brain metastasis development in patients with NSCLC without brain metastases at initial presentation. METHODS. This retrospective study included 1495 patients with NSCLC (mean [± SD] age, 65 ± 10 years; 920 men and 575 women) without brain metastases at initial evaluation that included brain MRI. Follow-up brain MRI was ordered at the discretion of the referring physicians. MRI examinations were reviewed in combination with clinical records for brain metastasis development; patients not undergoing MRI were deemed to have not had metastases develop through last clinical follow-up. The cumulative incidence of brain metastases was determined, with death considered a competing risk, and was stratified by clinical stage group, cell type, and epidermal growth factor receptor (EGFR) gene mutation status. Univariable and multivariable Cox proportional hazards regression analyses were performed. RESULTS. A total of 258 of 1495 patients (17.3%) underwent follow-up brain MRI, and 72 (4.8%) had brain metastases develop at a median of 12.3 months after initial diagnosis of NSCLC. Of the 72 patients who had metastases develop, 44.4% had no neurologic symptoms, and 58.3% had stable primary thoracic disease. The cumulative incidence of brain metastases at 6, 12, 18, and 24 months after initial evaluation was 0.6%, 2.1%, 4.2%, and 6.8%, respectively. Cumulative incidence at 6, 12, 18, and 24 months was higher (p < .001) in patients with clinical stage III-IV disease (1.3%, 3.9%, 7.7%, and 10.9%, respectively) than in those with clinical stage I-II disease (0.0%, 0.8%, 1.2%, and 2.6%, respectively), and it was higher (p < .001) in patients with EGFR mutation-positive adenocarcinoma (0.7%, 2.5%, 6.3%, and 12.3%, respectively) than in those with EGFR mutation-negative adenocarcinoma (0.4%, 1.8%, 2.9%, and 4.4%, respectively). Among 1109 patients with adenocarcinoma, independent risk factors for the development of brain metastasis were clinical stage III-IV (hazard ratio [HR], 9.39; p < .001) and EGFR mutation-positive status (HR, 1.78; p = .04). The incidence of brain metastasis over the study interval was 8.7% among patients with clinical stage III-IV disease and 17.4% among those with EGFR mutation-positive adenocarcinoma. CONCLUSION. Clinical stage III-IV and EGFR mutation-positive adenocarcinoma are independent risk factors for brain metastasis development. CLINICAL IMPACT. For patients with clinical stage III-IV disease or EGFR mutation-positive adenocarcinoma, surveillance brain MRI performed 12 months after initial evaluation may be warranted.