Panel-Reactive and Donor-Specific Antibodies before Lung Transplantation can Affect Outcomes in Korean Patients Receiving Lung Transplantation

Purpose: Data on the distribution and impact of panel reactive antibodies (PRA) and donor specific antibodies (DSA) before lung transplantation in Asia, especially multi-center-based data, are limited. This study evaluated the prevalence of and effects of PRA and DSA levels before lung transplantations on outcomes in Korean patients using nationwide multicenter registry data. Materials and methods: This study included 103 patients who received a lung transplant at five tertiary hospitals in South Korea between March 2015 and December 2017. Mortality, primary graft dysfunction (PGD), and bronchiolitis obliterans syndrome (BOS) were evaluated. Results: Sixteen patients had class I and/or class II PRAs exceeding 50%. Ten patients (9.7%) had DSAs with a mean fluorescence intensity (MFI) higher than 1000, six of whom had antibodies with a high MFI (≥2000). DSAs with high MFIs were more frequently observed in patients with high-grade PGD (≥2) than in those with no or low-grade (≤1) PGD. In the 47 patients who survived for longer than 9 months and were evaluated for BOS after the transplant, BOS was not related to DSA or PRA levels. One-year mortality was more strongly related to PRA class I exceeding 50% than that under 50% (0% vs. 16.7%, p=0.007). Conclusion: Preoperative DSAs and PRAs are related to worse outcomes after lung transplantation. DSAs and PRAs should be considered when selecting lung transplant recipients, and recipients who have preoperative DSAs with high MFI values and high PRA levels should be monitored closely after lung transplantation.ope

Low serum lymphocyte level is associated with poor exercise capacity and quality of life in chronic obstructive pulmonary disease

The purpose of this study was to evaluate the association of serum lymphocyte level with several clinical parameters in COPD. The study population included 451 COPD patients from the Korean Obstructive Lung Disease cohort study. Serum lymphocyte level was measured every year along with various clinical parameters, such as lung function, 6-min walking (6 MW) distance, quality of life using COPD assessment test (CAT) and St. George's Respiratory Questionnaire (SGRQ) scores, exacerbations, and survival. Serum lymphocyte level less than 20% was considered as a low lymphocyte level. Normal lymphocyte and low lymphocyte groups comprised of 409 (90.7%) and 42 (9.3%) patients, respectively. Clustered analysis showed that patients in low lymphocyte group had a lower post-bronchodilator forced expiratory volume in 1 s % predicted (estimated mean = - 5.70%; P = 0.001), a lower forced vital capacity % predicted (estimated mean = - 5.63%; P = 0.005), a shorter 6 MW distance (estimated mean = - 41.31 m; P < 0.001), a higher CAT score (estimated mean = 2.62; P = 0.013), and a higher SGRQ score (estimated mean = 10.10; P < 0.001). Serum lymphocyte level was not associated with frequent acute exacerbations nor mortality. Low serum lymphocyte group showed poorer pulmonary function, lower 6 MW distance, and worse quality of life. Serum lymphocyte levels could be a simple and widely available predictive marker for variable clinical outcomes in COPD patients.ope

Low muscle mass, low muscle function, and sarcopenia in the urban and rural elderly

Health outcomes of the elderly vary between rural and urban areas. Sarcopenia is diagnosed as loss of muscle strength or impaired physical performance, namely "low muscle function" and low muscle mass. Outcomes of low muscle mass and low muscle function are not equal. This study aimed to investigate the prevalence of low muscle mass, low muscle function, and sarcopenia in rural and urban populations and to determine whether regional differences were associated with each of these components. Participants aged ≥ 69 years (n = 2354) were recruited from three urban districts and one rural district in Korea. Low muscle mass was defined by appendicular lean mass using bioelectrical impedance analysis. Low muscle function was defined by handgrip strength and 5-chair stand test. Sarcopenia was defined as low muscle mass plus low muscle function. The prevalence of low muscle function (53.7% vs. 72.8%), and sarcopenia (16.3% vs. 24.4%) were higher in the rural elderly population. Rural residence was associated with low muscle function (OR 1.63; 95% CI 1.13-2.37, P = 0.009), but not with low muscle mass (OR 0.58; 95% CI 0.22-1.54, P = 0.271) or with sarcopenia (OR 1.13; 95% CI 0.63-2.00, P = 0.683). Interventions to detect and improve low muscle function in rural elderly population are needed.ope

Combined pulmonary fibrosis and emphysema and idiopathic pulmonary fibrosis in non-small cell lung cancer: impact on survival and acute exacerbation

BACKGROUND: In non-small cell lung cancer (NSCLC) patients, concomitant idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) are independently related to poor survival. CPFE is a condition with features of both pulmonary fibrosis and emphysema. Here, we evaluated the effect of CPFE and IPF alone on the outcomes of NSCLC patients. PATIENTS AND METHODS: We retrospectively evaluated 283 patients with CPFE or IPF who were diagnosed with NSCLC between November 2003 and February 2018 at two tertiary care hospitals in South Korea. Patients were classified into CPFE and IPF groups according to chest computed tomography findings. RESULTS: One-hundred-and-seven patients (37.8%; mean age: 70.1 years; men 97.2%) had CPFE. Compared with IPF patients, CPFE patients had a heavier smoking history; lower diffusing capacity of carbon monoxide (78.0% vs 64.8%, p  III NSCLC, higher Eastern Cooperative Oncology Group performance status, and higher gender-age-physiology index score was related to higher mortality. However, CPFE was not related to a higher mortality rate in univariate (hazard ratio [HR]: 1.00; 95% CI: 0.75-1.32, P = 0.972) or multivariate analysis (HR: 0.89; 95% CI: 0.66-1.21, P = 0.466). CONCLUSIONS: AE risk, but not all-cause mortality, was higher in patients with CPFE and NSCLC than in those with IPF and NSCLC. Physicians should be aware of the exaggerated risk of AE in patients with concomitant CPFE and NSCLC.ope

Etiologies and Underlying Diseases of Leg Edema in Elderly Patients

Background: Leg edema is a common symptom among elderly patients with multiple underlying diseases. This study was aimed to investigate the etiologies and underlying diseases of leg edema in elderly patients.Methods: We retrospectively reviewed medical records of 247 patients aged over 65, who visited an Emergency Department of a tertiary hospital due to leg edema from January 2010 to December 2012. Results: A total of 226 patients with complete medical records were included. The most common cause of leg edema in elderly patients was renal failure (42 cases, 18.6%), followed by heart failure (37 cases, 16.4%), and deep vein thrombosis (32 cases, 14.2%). However, the etiologies were not established in 66 cases (29.2%). Patients with leg edema caused by renal and heart failure had renal (40 cases, 95.2%) and cardiovascular diseases (29 cases, 78.4%), respectively, while others had diabetes mellitus and trauma. Patients with leg edema caused by deep vein thrombosis had underlying conditions such as cancer (13 cases, 40.6%), trauma, surgery within 1 year, and diabetes mellitus. Overall, chronic bilateral edema (120 cases, 53.1%) was most commonly observed form of leg edema in elderly patients. Deep vein thrombosis, cellulitis, and lymphedema usually caused unilateral edema, whereas systemic diseases such as renal failure, heart failure, and liver cirrhosis caused bilateral edema. Conclusion: Leg edema in elderly patients is usually caused by systemic diseases such as renal and heart failure closely related to underlying diseases. Therefore, it is important to consider the variety of underlying diseases, when approaching the cause and treatment of leg edema in elderly patients.ope

Thoracic skeletal muscle quantification using computed tomography and prognosis of elderly ICU patients

In elderly ICU patients, the prevalence of skeletal muscle loss is high. Longitudinal effect of thoracic muscles, especially in elderly ICU patients, are unclear although skeletal muscle loss is related with the short- and long-term outcomes. This study aimed to evaluate whether pectoralis muscle mass loss could be a predictor of prognosis in elderly ICU patients. We retrospectively evaluated 190 elderly (age > 70 years) patients admitted to the ICU. We measured the cross-sectional area (CSA) of the pectoralis muscle (PMCSA) at the fourth vertebral region. CT scans within two days before ICU admission were used for analysis. Mortality, prolonged mechanical ventilation, and longitudinal changes in Sequential Organ Failure Assessment (SOFA) scores were examined. PMCSA below median was significantly related with prolonged ventilation (odds ratio 2.92) and a higher SOFA scores during the ICU stay (estimated mean = 0.94). PMCSA below median was a significant risk for hospital mortality (hazards ratio 2.06). In elderly ICU patients, a low ICU admission PMCSA was associated with prolonged ventilation, higher SOFA score during the ICU stay, and higher mortality. Adding thoracic skeletal muscle CSA at the time of ICU admission into consideration in deciding the therapeutic intensity in elderly ICU patients may help in making medical decisions.ope

Relationship between obstructive lung disease and non-alcoholic fatty liver disease in the Korean population: Korea National Health and Nutrition Examination Survey, 2007-2010.

Purpose: Previous studies have shown that progressive forms of non-alcoholic fatty liver disease (NAFLD) occur frequently in patients with obstructive lung disease (OLD). However, few studies have written about this relationship. This study aimed to investigate the relationship between OLD and NAFLD. Subjects and methods: The Korea National Health and Nutrition Examination Survey is a national population-based, cross-sectional surveillance program that was initiated to assess the health and nutritional status of the Korean population. From 2007 to 2010, 11,738 subjects were enrolled. The subjects were defined as having NAFLD when they had scores higher than -0.640 in a NAFLD liver fat score prediction model, which was a previously validated prediction score. Individuals with forced expiratory volume in one second/forced vital capacity <0.7 were considered to have OLD. The subjects were divided into non-OLD and OLD groups and non-NAFLD and NAFLD groups. All analyses were performed using sample weighting using the complex samples plan. Results: The prevalences of NAFLD and OLD were 30.2% and 8.9%, respectively. Although not statistically significant, subjects in the NAFLD group involved a higher tendency of having OLD than did those in the non-NAFLD group (8.5% vs 10.0%, respectively, P=0.060). Subjects with OLD showed a higher tendency to have NAFLD than non-OLD subjects (30.0% vs 33.7%, respectively, P=0.060). NAFLD subjects were at higher odds of OLD (odds ratio=1.334; 95% confidence interval=1.108-1.607, P=0.002) than non-NAFLD subjects, after adjusting for age, sex, and smoking history. OLD subjects were at higher odds of NAFLD (odds ratio=1.556; 95% confidence interval=1.288-1.879, P<0.001) than non-OLD subjects, after adjusting for age, sex, and smoking history. Conclusion: This study showed that NAFLD is related to OLD. Clinicians should be aware of possible liver comorbidities in OLD patients and that extrahepatic disease in NAFLD patients may vary more than previously thought.ope

Hemophagocytic Lymphohistiocytosis after Lung Transplantation

Hemophagocytic lymphohistiocytosis (HLH) is a rare but fatal complication after solid organ transplantation. Acquired forms of HLH are described in association with severe sepsis, autoimmune disorders, malignancy, immune-compromised states, infections, and solid organ transplantation. We experienced a case of hemophagocytic lymphohistiocytosis after bilateral lung transplantation. Leukopenia, thrombocytopenia, and hyperbilirubinemia were noted and became aggravated 50 days after transplantation. Diagnosis of HLH was based on clinical and laboratory findings of splenomegaly, cytopenia, elevated ferritin, elevated interleukin-2 receptor, and hemophagocytosis in bone marrow. Other features such as elevated bilirubin, lactate dehydrogenase, and D-dimer which can be present in HLH were also noted. The patient was immediately treated with etoposide and dexamethasone. Despite aggressive therapy, the patient deteriorated and died. Awareness of the diagnostic criteria of HLH after lung transplantation is important for clinicians.ope

Thoracic skeletal muscle quantification: low muscle mass is related with worse prognosis in idiopathic pulmonary fibrosis patients

BACKGROUND: Sarcopenia can contribute to negative outcomes in patients with various lung diseases. However, whether sarcopenia affects prognosis in patients with idiopathic pulmonary fibrosis (IPF) has not been reported. Simple measures of muscle mass, derived from chest computed tomography (CT), are increasingly being used to identify patients with sarcopenia. We hypothesized that skeletal muscle mass could be a predictor of prognosis in IPF patients. METHODS: We retrospectively evaluated 180 patients diagnosed with IPF between January 2010 and December 2015 at a tertiary care hospital in South Korea. We measured thoracic muscle volume by using the cross-sectional area (CSA) of the pectoralis, paraspinal, serratus, and latissimus muscles at the 4th vertebral region (T4CSA) and the erector spinae muscle (ESMCSA) at the 12th vertebral region. CT scans at the time of diagnosis were used for analysis and respective CSA were divided by height squared to normalize for stature. Survival times were estimated with the Kaplan-Meier method and compared with the log-rank test. Multivariate Cox proportional hazards models were performed to investigate relationships between clinical parameters and mortality. RESULTS: Male patients in the lowest quartile of T4CSA divided by height squared (m2) (T4MI) and in the lowest quartile of ESMCSA divided by height squared (m2) (T12MI) were more likely to have higher Gender-Age-Physiology Index scores (T4MI, 3.3 ± 1.3 vs 4.0 ± 1.6, P = 0.012; T12MI, 3.2 ± 1.3 vs 4.1 ± 1.6, P = 0.002). Male patients in the lowest quartile of T4MI exhibited a significantly lower survival rate (P = 0.035). After multivariate Cox proportional hazards analysis, T4MI was a significant risk factor for all-cause mortality (HR, 0.955; 95% CI, 0.913-0.998; P = 0.041), whereas T12MI was not (HR, 0.980; 95% CI, 0.856-1.121; P = 0.766). CONCLUSIONS: Low skeletal mass normalized for stature at the level of 4th vertebrae which can be acquired by quantifying thoracic skeletal muscle on single-slice axial chest CT, may be a strong risk factor for all-cause mortality in patients with IPF. TRIAL REGISTRATION: The research protocol was approved by the Institutional Review Board of Severance Hospital, South Korea (IRB No.4-2018-0454).ope

Risk factors and outcome of primary graft dysfunction after lung transplantation in Korea

BACKGROUND: Primary graft dysfunction (PGD) is a severe, acute and post-transplantation lung injury associated with early morbidity and mortality. We aimed to identify clinical risk factors for PGD, as well as the outcome of PGD after lung transplantation in Korea. METHODS: We retrospectively analyzed lung transplant patients in a South Korean Hospital. The primary outcome was grade 3 PGD, defined according to the International Society for Heart and Lung Transplantation criteria. We compared grade 0-2 PGD group to grade 3 PGD group to identify the risk factors and outcome of grade 3 PGD. RESULTS: Sixty-one patients were enrolled; 16 (26.2%) developed grade 3 PGD. Univariate analysis revealed higher body mass index (BMI) and history of smoking, extracorporeal membrane oxygenation (ECMO) before transplantation in recipients, and an extended intraoperative ischemic time as risk factors for grade 3 PGD. In multivariate analysis, independent risk factors for PGD were higher BMI in recipients [odds ratio (OR), 1.286; P=0.043] and total intraoperative ischemic time (OR, 1.028; P=0.007). As compared to grade 0-2 PGD, grade 3 PGD was significantly associated with a higher re-operation rate (grade 0-2 PGD vs. grade 3 PGD, 22.2% vs. 50.0%; P=0.036), prolonged ventilator apply (median: 6.0 vs. 14.5 days; P=0.044), a longer intensive care unit stay (median: 9.0 vs. 17.0 days; P=0.041), and a higher rate of renal replacement therapy (RRT) (17.8% vs. 62.5%; P=0.002) after transplantation. CONCLUSIONS: Patients who developed grade 3 PGD had higher re-operation rate, longer ventilator apply, longer intensive care unit stay, higher rate of RRT, with higher BMI and total intraoperative ischemic time being the significant risk factor. These findings may allow physicians to modify risk factors before development of PGD.ope