Nailfold capillaroscopy findings of interstitial pneumonia with autoimmune features

Background/Aims@#We evaluated nailfold capillaroscopy (NFC) of interstitial pneumonia with autoimmune features (IPAF) and compared it with that of patients with connective tissue disease-interstitial lung disease (CTD-ILD) and idiopathic interstitial pneumonia (IIP). @*Methods@#Patients with newly diagnosed as ILD were evaluated using NFC. Baseline demographic, clinical, serological, and high-resolution CT findings were collected. NFC was semi-quantitatively scored with six domains ranging from 0 to 18. In addition, the overall patterns (sclerodermaon-scleroderma patterns) were determined. @*Results@#A total of 81 patients (31 with CTD-ILD, 18 with IPAF, and 32 with IIP) were included. The non-specific interstitial pneumonia pattern was the most common ILD pattern in the CTD-ILD and IPAF groups, whereas the usual interstitial pneumonia pattern was the most common in the IIP group. The semi-quantitative score of the CTD-ILD group was higher than that of the IPAF or IIP groups (5.8 vs 4.2 vs 3.0, p < 0.001, respectively). Giant capillaries and haemorrhages were more frequently present in the CTD-ILD and IPAF groups than in the IIP group. A scleroderma pattern was present in 27.8% of the IPAF group, whereas none of the IIP patients showed a scleroderma pattern. @*Conclusions@#NFC findings may be useful in classifying patients with ILD into CTD-ILD/IPAF/IIP.

COVID-19 Vaccine-Associated Pneumonitis in the Republic of Korea:A Nationwide Multicenter Survey

Background@#Recent reports have suggested that pneumonitis is a rare complication following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).However, its clinical features and outcomes are not well known. The aim of this study was to identify the clinical characteristics and outcomes of patients with vaccine-associated pneumonitis following vaccination against SARS-CoV-2. @*Methods@#In this nationwide multicenter survey study, questionnaires were distributed to pulmonary physicians in referral hospitals. They were asked to report cases of development or exacerbation of interstitial lung disease (ILD) associated with the coronavirus disease 2019 vaccine. Vaccine-associated pneumonitis was defined as new pulmonary infiltrates documented on chest computed tomography within 4 weeks of vaccination and exclusion of other possible etiologies. @*Results@#From the survey, 49 cases of vaccine-associated pneumonitis were identified between February 27 and October 30, 2021. After multidisciplinary discussion, 46 cases were analyzed. The median age was 66 years and 28 (61%) were male. The median interval between vaccination and respiratory symptoms was 5 days. There were 20 (43%), 17 (37%), and nine (19%) patients with newly identified pneumonitis, exacerbation of pre-diagnosed ILD, and undetermined pre-existing ILD, respectively. The administered vaccines were BNT162b2 and ChAdOx1 nCov-19/AZD1222 each in 21 patients followed by mRNA-1273 in three, and Ad26.COV2.S in one patient. Except for five patients with mild disease, 41 (89%) patients were treated with corticosteroid. Significant improvement was observed in 26 (57%) patients including four patients who did not receive treatment. However, ILD aggravated in 9 (20%) patients despite treatment. Mortality was observed in eight (17%) patients. @*Conclusion@#These results suggest pneumonitis as a potentially significant safety concern for vaccines against SARS-CoV-2. Clinical awareness and patient education are necessary for early recognition and prompt management. Additional research is warranted to identify the epidemiology and characterize the pathophysiology of vaccine-associated pneumonitis.

Efficacy of lower dose pirfenidone for idiopathic pulmonary fibrosis in real practice: a retrospective cohort study

Background/Aims@#Pirfenidone slows the progression of idiopathic pulmonary fibrosis (IPF). We investigated its efficacy and safety in terms of dose and disease severity in real-world patients with IPF. @*Methods@#This multicenter retrospective cohort study investigated 338 patients treated with pirfenidone between July 2012 and March 2018. Demographics, pulmonary function, mortality, and pirfenidone-related adverse events were also investigated. Efficacy was analyzed according to pirfenidone dose and disease severity using linear mixed-effects models to assess the annual decline rate of forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO). @*Results@#The mean %FVCpredicted and %DLCOpredicted values were 72.6% ± 13.1% and 61.4% ± 17.9%, respectively. The mean duration of pirfenidone treatment was 16.1 ± 9.0 months. In the standard dose (1,800 mg/day) group, the mean %FVCpredicted was −6.56% (95% confidence interval [CI], −9.26 to −3.87) per year before, but −4.43% (95% CI, −5.87 to −3.00) per year after treatment with pirfenidone. In the non-standard lower dose group, the mean %FVCpredicted was −4.96% (95% CI, −6.82 to −3.09) per year before, but −1.79% (95% CI, −2.75 to −0.83) per year after treatment with pirfenidone. The FVC decline rate was significantly reduced, regardless of the Gender-Age-Physiology (GAP) stage. Adverse events and mortality were similar across dose groups; however, they were more frequent in GAP stages II–III than in the stage I group. @*Conclusions@#The effect of pirfenidone on reducing disease progression of IPF persisted even with a consistently lower dose of pirfenidone.

Prevalence and impact of airway diseases on clinical outcomes in idiopathic pulmonary fibrosis

Background/Aims@#The prevalence and effects of airway diseases, including asthma, eosinophilic bronchitis (EB), chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) have not been thoroughly studied in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to evaluate the prevalence of airway diseases in patients with IPF and to identify the differences in symptoms based on the presence of airway diseases. @*Methods@#This single-institution prospective cohort study was conducted from June 2017 to September 2018, at the Seoul National University Hospital. Spirometry with bronchodilator, methacholine bronchial provocation test, induced sputum with eosinophil stain, and exhaled nitric oxide were performed to confirm the presence of airway disease. The modified Medical Research Council (mMRC) dyspnea scale, COPD assessment test (CAT), St. George’s Respiratory Questionnaire (SGRQ), EuroQol-5 dimension (EQ-5D) index, and cough-specific quality of life questionnaire (CQLQ) data were collected to assess symptom severity. @*Results@#Total 147 patients with IPF were screened, and 70 patients were analyzed. The prevalence of airway diseases in the participants was as follows: 5.0% had COPD, 1.7% had asthma, 3.3% had ACO, and 1.7% had EB. The mMRC, CAT, SGRQ, EQ-5D, and CQLQ scores did not differ regardless of combined airway disease. After 3 months, the SGRQ (p = 0.028) and CQLQ (p = 0.030) scores were significantly higher in patients with airway disease than in those without. @*Conclusions@#The prevalence of airway diseases in patients with IPF is low, but when airway diseases are accompanied by IPF, symptom severity and quality of life may worsen rapidly.

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 2. Idiopathic Pulmonary Fibrosis / 결핵

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, which presents with a progressive worsening dyspnea, and thus a poor outcome. The members of the Korean Academy of Tuberculosis and Respiratory Diseases as well as the participating members of the Korea Interstitial Lung Disease Study Group drafted this clinical practice guideline for IPF management. This guideline includes a wide range of topics, including the epidemiology, pathogenesis, risk factors, clinical features, diagnosis, treatment, prognosis, and acute exacerbation of IPF in Korea. Additionally, we suggested the PICO for the use of pirfenidone and nintendanib and for lung transplantation for the treatment of patients with IPF through a systemic literature review using experts' help in conducting a meta-analysis. We recommend this guideline to physicians, other health care professionals, and government personnel in Korea, to facilitate the treatment of patients with IPF.

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 2. Idiopathic Pulmonary Fibrosis / 결핵및호흡기질환

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, which presents with a progressive worsening dyspnea, and thus a poor outcome. The members of the Korean Academy of Tuberculosis and Respiratory Diseases as well as the participating members of the Korea Interstitial Lung Disease Study Group drafted this clinical practice guideline for IPF management. This guideline includes a wide range of topics, including the epidemiology, pathogenesis, risk factors, clinical features, diagnosis, treatment, prognosis, and acute exacerbation of IPF in Korea. Additionally, we suggested the PICO for the use of pirfenidone and nintendanib and for lung transplantation for the treatment of patients with IPF through a systemic literature review using experts' help in conducting a meta-analysis. We recommend this guideline to physicians, other health care professionals, and government personnel in Korea, to facilitate the treatment of patients with IPF.

Utility of the National Lung Screening Trial Criteria for Estimation of Lung Cancer in the Korean Population / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Screening forlung cancerin high-risk patients using the National Lung Screening Trial (NLST) criteria resulted in a decreased lung cancer-related mortality rate. However, whether these criteria are applicable to the Korean has not been investigated thus far. Therefore, we estimated the utility of the NLST criteria as a screening tool for lung cancer in the Korean population. MATERIALS AND METHODS: The total number of newly diagnosed lung cancer cases in 2013 was obtained from the Korea National Statistical Office. The proportion of newly diagnosed lung cancer cases that met the NLST criteria was calculated via a retrospective cohort of a tertiary referral hospital. We estimated the nationwide proportion of patients who met the NLST criteria using the 5th Korea National Health and Nutrition Examination Survey conducted during 2010-2012 (KNHANES V). RESULTS: Using KNHANES V data, we found that approximately 6.92% of the general population of Korea would meet the NLST criteria. In the tertiary referral hospital, 29.6% of the 2,689 newly diagnosed lung cancer patients met the NLST criteria. In 2013, the total number of newly diagnosed lung cancer cases in Korea was 23,177. The estimated nationwide proportions of lung cancer patients who met and did not meet the NLST criteria were 0.37% and 0.06%, respectively, yielding a ratio of 5.78. CONCLUSION: The NLST criteria demonstrated sound clinical utility for lung cancer screening of high-risk patients in Korea.

Histopathologic heterogeneity of acute respiratory distress syndrome revealed by surgical lung biopsy and its clinical implications

BACKGROUND/AIMS: Diffuse alveolar damage (DAD) is the histopathologic hallmark of acute respiratory distress syndrome (ARDS). However, there are several non-DAD conditions mimicking ARDS. The purpose of this study was to investigate the histopathologic heterogeneity of ARDS revealed by surgical lung biopsy and its clinical relevance. METHODS: We retrospectively analyzed 84 patients with ARDS who met the criteria of the Berlin definition and underwent surgical lung biopsy between January 2004 and December 2013 in three academic hospitals in Korea. We evaluated their histopathologic findings and compared the clinical outcomes. Additionally, the impact of surgical lung biopsy on therapeutic alterations was examined. RESULTS: The histopathologic findings were highly heterogeneous. Of 84 patients undergoing surgical lung biopsy, DAD was observed in 31 patients (36.9%), while 53 patients (63.1%) did not have DAD. Among the non-DAD patients, diffuse interstitial lung diseases and infections were the most frequent histopathologic findings in 19 and 17 patients, respectively. Although the mortality rate was slightly higher in DAD (71.0%) than in non-DAD (62.3%), the difference was not significant. Overall, the biopsy results led to treatment alterations in 40 patients (47.6%). Patients with non-DAD were more likely to change the treatment than those with DAD (58.5% vs. 29.0%), but there were no significant improvements regarding the mortality rate. CONCLUSIONS: The histopathologic findings of ARDS were highly heterogeneous and classic DAD was observed in one third of the patients who underwent surgical lung biopsy. Although therapeutic alterations were more common in patients with non-DAD-ARDS, there were no significant improvements in the mortality rate.

Effect of Preadmission Metformin Use on Clinical Outcome of Acute Respiratory Distress Syndrome among Critically Ill Patients with Diabetes / 결핵및호흡기질환

BACKGROUND: Acute respiratory distress syndrome (ARDS) is related to high mortality and morbidity. There are no proven therapeutic measures however, to improve the clinical course of ARDS, except using low tidal volume ventilation. Metformin is known to have pleiotropic effects including anti-inflammatory activity. We hypothesized that pre-admission metformin might alter the progress of ARDS among intensive care unit (ICU) patients with diabetes mellitus (DM). METHODS: We performed a retrospective cohort study from January 1, 2005, to April 30, 2005 of patients who were admitted to the medical ICU at Seoul National University Hospital because of ARDS, and reviewed ARDS patients with DM. Metformin use was defined as prescribed within 3-month pre-admission. RESULTS: Of 558 patients diagnosed with ARDS, 128 (23.3%) patients had diabetes and 33 patients were treated with metformin monotherapy or in combination with other antidiabetic medications. Demographic characteristics, cause of ARDS, and comorbid conditions (except chronic kidney disease) were not different between metformin users and nonusers. Several severity indexes of ARDS were similar in both groups. The 30-day mortality was 42.42% in metformin users and 55.32% in metformin nonusers. On multivariable regression analysis, use of metformin was not significantly related to a reduced 30-day mortality (adjusted β-coefficient, −0.19; 95% confidence interval, −1.76 to 1.39; p=0.816). Propensity score-matched analyses showed similar results. CONCLUSION: Pre-admission metformin use was not associated with reduced 30-day mortality among ARDS patients with DM in our medical ICU.

Effect of Renin-Angiotensin System Blockage in Patients with Acute Respiratory Distress Syndrome: A Retrospective Case Control Study / 대한중환자의학회지

BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a life-threatening disease. Many patients with ARDS do not recover fully, and progress to terminal lung fibrosis. Angiotensin-converting enzyme (ACE) inhibitor is known to modulate the neurohormonal system to reduce inflammation and to prevent tissue fibrosis. However, the role of ACE inhibitor in the lungs is not well understood. We therefore conducted this study to elucidate the effect of renin-angiotensin system (RAS) blockage on the prognosis of patients with ARDS. METHODS: We analyzed medical records of patients who were admitted to the medical intensive care unit (ICU) at a tertiary care hospital from January 2005 to December 2010. ARDS was determined using the Berlin definition. The primary outcome was the mortality rate of ICU. Survival analysis was performed after adjustment using propensity score matching. RESULTS: A total of 182 patients were included in the study. Thirty-seven patients (20.3%) took ACE inhibitor or angiotensin receptor blocker (ARB) during ICU admission, and 145 (79.7%) did not; both groups showed similar severity scores. In the ICU, mortality was 45.9% in the RAS inhibitor group and 58.6% in the non-RAS inhibitor group (P = 0.166). The RAS inhibitor group required a longer duration of mechanical ventilation (29.5 vs. 19.5, P = 0.013) and longer ICU stay (32.1 vs. 20.2 days, P < 0.001). In survival analysis, the RAS inhibitor group showed better survival rates than the non-RAS group (P < 0.001). CONCLUSIONS: ACE inhibitor or ARB may have beneficial effect on ARDS patients.

Medical Thoracoscopy in Pleural Disease: Experience from a One-Center Study / 결핵및호흡기질환

BACKGROUND: Medical thoracoscopy (MT) is a minimally invasive, endoscopic procedure for exploration of the pleural cavity under conscious sedation and local anesthesia. MT has been performed at the Seoul National University Hospital since February 2014. This paper summarizes the findings and outcomes of MT cases at this hospital. METHODS: Patients who had undergone MT were enrolled in the study. MT was performed by pulmonologists, using both rigid and semi-rigid thoracoscopes. During the procedure, patients were under conscious sedation with fentanyl and midazolam. Medical records were reviewed for clinical data. RESULTS: From February 2014 to January 2016, 50 procedures (47 cases) were performed (diagnostic MT, 26 cases; therapeutic MT, 24 cases). The median age of patients was 66 years (59–73 years), and 38 patients (80.9%) were male. The median procedure duration from initial incision to insertion of the chest tube was 37 minutes. The median doses of fentanyl and midazolam were 50 µg and 5 mg, respectively. All procedures were performed without unexpected events. Of the 26 cases of pleural disease with an unknown cause, 19 were successfully diagnosed using MT. Additionally, diagnostic MT provided clinically useful information in the other six patients. Therapeutic MT was very effective for treatment of malignant pleural effusion or empyema. The median number of days with chest tube drainage was 6 (3 days for diagnostic MT and 8 days for therapeutic MT). CONCLUSION: MT is a useful and necessary procedure for both diagnosis and treatment of pleural diseases.

Analysis of Fifty Hotspot Mutations of Lung Squamous Cell Carcinoma in Never-smokers

Smoking is the major risk factor for lung squamous cell carcinoma (SCC), although a small number of lung SCCs occurs in never-smokers. The purpose of this study was to compare 50 hotspot mutations of lung SCCs between never-smokers and smokers. We retrospectively reviewed the medical records of patients newly diagnosed with lung SCC between January 1, 2011 and December 31, 2013 in the Seoul National University Hospital. Formalin-fixed, paraffin-embedded tumor samples were used for analysis of hotspot mutations. Fifty cancer-related genes in never-smokers were compared to those in ever-smokers. Of 379 lung SCC patients, 19 (5.0%) were never-smokers. The median age of these 19 patients was 67 years (interquartile range 57–73 years), and 10 of these patients were women (52.5%). The incidence rates of stage I, II, III, and IV disease in this group were 26.4%, 5.3%, 31.6%, and 36.8%, respectively, and sequencing was performed successfully in 14 cases. In the 26 lung SCC tumor samples (12 from never-smokers and 14 from ever-smokers) sequenced using personal genome machine, the most common mutations were in TP53 (75.0%), RAS (66.7%), and STK11 (33.3%), but mutations were also found in EGFR, KIT, and PTEN. The distribution of hotspot mutations in never-smokers was similar to that in ever-smokers. There was no significant difference in overall survival between the 2 groups. The 50 hotspot mutations of lung SCC in never-smokers were similar to those of ever-smokers.

Incidence of Fever Following Endobronchial Ultrasound–Guided Transbronchial Needle Aspiration / 결핵및호흡기질환

BACKGROUND: Endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive diagnostic method for mediastinal and hilar lymphadenopathy. This study aimed to investigate the incidence of fever following EBUS-TBNA. METHODS: A total of 684 patients who underwent EBUS-TBNA from May 2010 to July 2012 at Seoul National University Hospital were retrospectively reviewed. The patients were evaluated for fever by a physician every 6–8 hours during the first 24 hours following EBUS-TBNA. Fever was defined as an increase in axillary body temperature over 37.8℃. RESULTS: Fever after EBUS-TBNA developed in 110 of 552 patients (20%). The median onset time and duration of fever was 7 hours (range, 0.5–32 hours) after EBUS-TBNA and 7 hours (range, 1–52 hours), respectively, and the median peak body temperature was 38.3℃ (range, 37.8–39.9℃). In most patients, fever subsided within 24 hours; however, six cases (1.1%) developed fever lasting longer than 24 hours. Infectious complications developed in three cases (0.54%) (pneumonia, 2; mediastinal abscess, 1), and all three patients had diabetes mellitus. The number or location of sampled lymph nodes and necrosis of lymph node were not associated with fever after EBUS-TBNA. Multiple logistic regression analysis did not reveal any risk factors for developing fever after EBUS-TBNA. CONCLUSION: Fever is relatively common after EBUS-TBNA, but is transient in most patients. However, clinicians should be aware of the possibility of infectious complications among patients with diabetes mellitus.

Successful Lung Transplantation in a Patient with Myasthenia Gravis

A 47-year-old man with myasthenia gravis (MG) was admitted for a lung transplant. He had bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation due to acute myeloid leukemia. MG developed after stem cell transplantation. Bilateral sequential lung transplantations and a total thymectomy were performed. The patient underwent right diaphragmatic plication simultaneously due to preoperatively diagnosed right diaphragmatic paralysis. A tracheostomy was performed and bilevel positive airway pressure (BiPAP) was applied on postoperative days 8 and 9, respectively. The patient was transferred to the general ward on postoperative day 12, successfully weaned off BiPAP on postoperative day 18, and finally discharged on postoperative day 62.

Successful Lung Transplantation in a Patient with Myasthenia Gravis

A 47-year-old man with myasthenia gravis (MG) was admitted for a lung transplant. He had bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation due to acute myeloid leukemia. MG developed after stem cell transplantation. Bilateral sequential lung transplantations and a total thymectomy were performed. The patient underwent right diaphragmatic plication simultaneously due to preoperatively diagnosed right diaphragmatic paralysis. A tracheostomy was performed and bilevel positive airway pressure (BiPAP) was applied on postoperative days 8 and 9, respectively. The patient was transferred to the general ward on postoperative day 12, successfully weaned off BiPAP on postoperative day 18, and finally discharged on postoperative day 62.

Effect of Renin-Angiotensin System Blockage in Patients with Acute Respiratory Distress Syndrome: A Retrospective Case Control Study / 대한구급학회지

BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a life-threatening disease. Many patients with ARDS do not recover fully, and progress to terminal lung fibrosis. Angiotensin-converting enzyme (ACE) inhibitor is known to modulate the neurohormonal system to reduce inflammation and to prevent tissue fibrosis. However, the role of ACE inhibitor in the lungs is not well understood. We therefore conducted this study to elucidate the effect of renin-angiotensin system (RAS) blockage on the prognosis of patients with ARDS. METHODS: We analyzed medical records of patients who were admitted to the medical intensive care unit (ICU) at a tertiary care hospital from January 2005 to December 2010. ARDS was determined using the Berlin definition. The primary outcome was the mortality rate of ICU. Survival analysis was performed after adjustment using propensity score matching. RESULTS: A total of 182 patients were included in the study. Thirty-seven patients (20.3%) took ACE inhibitor or angiotensin receptor blocker (ARB) during ICU admission, and 145 (79.7%) did not; both groups showed similar severity scores. In the ICU, mortality was 45.9% in the RAS inhibitor group and 58.6% in the non-RAS inhibitor group (P = 0.166). The RAS inhibitor group required a longer duration of mechanical ventilation (29.5 vs. 19.5, P = 0.013) and longer ICU stay (32.1 vs. 20.2 days, P < 0.001). In survival analysis, the RAS inhibitor group showed better survival rates than the non-RAS group (P < 0.001). CONCLUSIONS: ACE inhibitor or ARB may have beneficial effect on ARDS patients.

Bleeding complications in critically ill patients with liver cirrhosis

BACKGROUND/AIMS: Patients with liver cirrhosis (LC) are at risk for critical events leading to Intensive Care Unit (ICU) admission. Coagulopathy in cirrhotic patients is complex and can lead to bleeding as well as thrombosis. The aim of this study was to investigate bleeding complications in critically ill patients with LC admitted to a medical ICU (MICU). METHODS: All adult patients admitted to our MICU with a diagnosis of LC from January 2006 to December 2012 were retrospectively assessed. Patients with major bleeding at the time of MICU admission were excluded from the analysis. RESULTS: A total of 205 patients were included in the analysis. The median patient age was 62 years, and 69.3% of the patients were male. The most common reason for MICU admission was acute respiratory failure (45.4%), followed by sepsis (27.3%). Major bleeding occurred in 25 patients (12.2%). The gastrointestinal tract was the most common site of bleeding (64%), followed by the respiratory tract (20%). In a multivariate analysis, a low platelet count at MICU admission (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99) and sepsis (OR, 8.35; 95% CI, 1.04 to 67.05) were independent risk factors for major bleeding. The ICU fatality rate was significantly greater among patients with major bleeding (84.0% vs. 58.9%, respectively; p = 0.015). CONCLUSIONS: Major bleeding occurred in 12.2% of critically ill cirrhotic patients admitted to the MICU. A low platelet count at MICU admission and sepsis were associated with an increased risk of major bleeding during the MICU stay. Further study is needed to better understand hemostasis in critically ill patients with LC.

Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations

BACKGROUND/AIMS: Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. METHODS: A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. RESULTS: In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p < 0.001) were poor prognostic factors for PFS. Among them, BMI and PNI were independent in multi-variable analysis. All of these were also significant prognostic values for OS. The higher the sum of scores, the poorer PFS and OS were observed. CONCLUSIONS: Pretreatment nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.

Metformin Reduces Bleomycin-induced Pulmonary Fibrosis in Mice

Metformin has anti-inflammatory and anti-fibrotic effects. We investigated whether metformin has an inhibitory effect on bleomycin (BLM)-induced pulmonary fibrosis in a murine model. A total of 62 mice were divided into 5 groups: control, metformin (100 mg/kg), BLM, and BLM with metformin (50 mg/kg or 100 mg/kg). Metformin was administered to the mice orally once a day from day 1. We sacrificed half of the mice on day 10 and collected the bronchoalveolar lavage fluid (BALF) from their left lungs. The remaining mice were sacrificed and analyzed on day 21. The right lungs were harvested for histological analyses. The messenger RNA (mRNA) levels of epithelial-mesenchymal transition markers were determined via analysis of the harvested lungs on day 21. The mice treated with BLM and metformin (50 mg/kg or 100 mg/kg) showed significantly lower levels of inflammatory cells in the BALF compared with the BLM-only mice on days 10 and 21. The histological examination revealed that the metformin treatment led to a greater reduction in inflammation than the treatment with BLM alone. The mRNA levels of collagen, collagen-1, procollagen, fibronectin, and transforming growth factor-β in the metformin-treated mice were lower than those in the BLM-only mice on day 21, although statistical significance was observed only in the case of procollagen due to the small number of live mice in the BLM-only group. Additionally, treatment with metformin reduced fibrosis to a greater extent than treatment with BLM alone. Metformin suppresses the inflammatory and fibrotic processes of BLM-induced pulmonary fibrosis in a murine model.

Trends in the Use of Intensive Care by Very Elderly Patients and Their Clinical Course in a Single Tertiary Hospital in Korea / 대한중환자의학회지

BACKGROUND: The number of elderly patients admitted to intensive care units (ICUs) is growing with the increasing proportion of elderly persons in the Korean general population. It is often difficult to make decisions about ICU care for elderly patients, especially when they are in their 90s. Data regarding the proportion of elderly patients in their 90s along with their clinical characteristics in ICU are scarce. METHODS: The records of Korean patients > or = 90 years old who were admitted to the medical ICU in a tertiary referral hospital between January 2005 and December 2014 were retrospectively reviewed. We compared the trend in ICU use and characteristics of these elderly patients between 2005-2009 and 2010-2014. RESULTS: Among 6,186 referred patients, 55 aged > or = 90 years were admitted to the medical ICU from 2005 to 2014. About 58.2% of these patients were male, and their mean age was 92.7 years. Their median Charlson comorbidity index score was 2 (IQR 1-3) and their mean APACHE II score was 25.0 (IQR 19.0-34.0). The most common reason for ICU care was acute respiratory failure. There were no differences in the survival rates between the earlier and more recent cohorts. However, after excluding patients who had specified "do not resuscitate" (DNR), the more recent group showed a significantly higher survival rate (53.8% mortality for the earlier group and 0% mortality for the recent group). Among the survivors, over half were discharged to their homes. More patients in the recent cohort (n=26 [78.8%]) specified DNR than in the earlier cohort (n=7 [35.0%], p=0.004). The number and proportion of patients > or = 90 years old among patients using ICU during the 2005-2014 study period did not differ. CONCLUSIONS: The use of ICU care by elderly patients > or = 90 years old was consistent from 2005-2014. The overall mortality rate tended to decrease, but this was not statistically significant. However, the proportion of patients specifying DNR was higher among more recent patients, and the recent group showed an even better survivorship after sensitivity analysis excluded patients specifying DNR.