The effect of nebulized N-acetylcysteine on the phlegm of chronic obstructive pulmonary disease: the NEWEST study.

BACKGROUND: Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. METHODS: This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score. RESULTS: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported. CONCLUSION: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks.

Predicting Successful Weaning through Sonographic Measurement of the Rapid Shallow Breathing Index.

Background: Diaphragmatic dysfunction correlates with weaning failure, highlighting the need to independently assess the diaphragm's effects on weaning. We modified the rapid shallow breathing index (RSBI), a predictor of successful weaning, by incorporating temporal variables into existing ultrasound-derived diaphragm index to create a simpler index closer to tidal volume. Methods: We conducted a prospective observational study of patients who underwent a spontaneous breathing trial in the medical intensive care unit (ICU) at Severance Hospital between October 2022 and June 2023. Diaphragmatic displacement (DD) and diaphragm inspiratory time (Ti) were measured using lung ultrasonography. The modified RSBI was defined as follows: respiratory rate (RR) divided by DD was defined as D-RSBI, and RR divided by the sum of the products of DD and Ti on both sides was defined as DTi-RSBI. Results: Among the sonographic indices, DTi-RSBI had the highest area under the receiver operating characteristic (ROC) curve of 0.774 in ROC analysis, and a correlation was found between increased DTi-RSBI and unsuccessful extubation in a multivariable logistic regression analysis (adjusted odds ratio 0.02, 95% confidence interval 0.00-0.97). Conclusions: The DTi-RSBI is beneficial in predicting successful weaning in medical ICU patients.

Clinical Characteristics and Treatment Outcomes of Pulmonary Diseases Caused by Coinfections With Multiple Nontuberculous Mycobacterial Species.

BACKGROUND: Coinfections with multiple nontuberculous mycobacterial (NTM) species have not been widely studied. We aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-pulmonary disease (PD) caused by coinfection with multiple NTM species. METHODS: We retrospectively reviewed patients with NTM-PD at a tertiary referral hospital in Korea between March 2012 and December 2018. Coinfection was defined as two or more species of NTM pathogens isolated from the same respiratory specimen or different specimens within three months. RESULTS: Among 1,009 patients with NTM-PD, 147 (14.6%) NTM coinfections were observed (average age 64.7 years, 69.4% women). NTM species were identified more frequently (median 6 vs. 3 times, P < 0.001) in the coinfection group than in the single species group, and follow-up duration was also longer in the coinfection group (median 44.9 vs. 27.1 months, P < 0.001). Mycobacterium avium complex (MAC) and M. abscessus and M. massiliense (MAB) were the dominant combinations (n = 71, 48.3%). For patients treated for over six months in the MAC plus MAB group (n = 31), sputum culture conversion and microbiological cure were achieved in 67.7% and 41.9% of patients, respectively. We divided the MAC plus MAB coinfection group into three subgroups according to the target mycobacteria; however, no statistical differences were found in the treatment outcomes. CONCLUSION: In NTM-PD cases, a significant number of multiple NTM species coinfections occurred. Proper identification of all cultured NTM species through follow-up is necessary to detect multispecies coinfections. Further research is needed to understand the nature of NTM-PD in such cases.

Development and validation of novel simple prognostic model for predicting mortality in Korean intensive care units using national insurance claims data.

BACKGROUND/AIMS: Intensive care unit (ICU) quality is largely determined by the mortality rate. Therefore, we aimed to develop and validate a novel prognostic model for predicting mortality in Korean ICUs, using national insurance claims data. METHODS: Data were obtained from the health insurance claims database maintained by the Health Insurance Review and Assessment Service of South Korea. From patients who underwent the third ICU adequacy evaluation, 42,489 cases were enrolled and randomly divided into the derivation and validation cohorts. Using the models derived from the derivation cohort, we analyzed whether they accurately predicted death in the validation cohort. The models were verified using data from one general and two tertiary hospitals. RESULTS: Two severity correction models were created from the derivation cohort data, by applying variables selected through statistical analysis, through clinical consensus, and from performing multiple logistic regression analysis. Model 1 included six categorical variables (age, sex, Charlson comorbidity index, ventilator use, hemodialysis or continuous renal replacement therapy, and vasopressor use). Model 2 additionally included presence/absence of ICU specialists and nursing grades. In external validation, the performance of models 1 and 2 for predicting in-hospital and ICU mortality was not inferior to that of pre-existing scoring systems. CONCLUSION: The novel and simple models could predict in-hospital and ICU mortality and were not inferior compared to the pre-existing scoring systems.

Differences of respiratory mechanics in mechanical ventilation of acute respiratory distress syndrome between patients with COVID-19 and Influenza A.

BACKGROUND: Whether COVID-19-induced acute respiratory distress syndrome (ARDS) should be approached differently in terms of mechanical ventilation therapy compared to other virus-induced ARDS is debatable. Therefore, we aimed to ascertain whether the respiratory mechanical characteristics of COVID-19-induced ARDS differ from those of influenza A induced ARDS, in order to establish a rationale for mechanical ventilation therapy in COVID-19-induced ARDS. METHODS: This was a retrospective cohort study comparing patients with COVID-19-induced ARDS and influenza A induced ARDS. We included intensive care unit (ICU) patients with COVID-19 or Influenza A aged ≥ 19, who were diagnosed with ARDS according to the Berlin definition between January 2015 and July 2021. Ventilation parameters for respiratory mechanics were collected at specific times on days one, three, and seven after intubation. RESULTS: The median age of the 87 participants was 71.0 (62.0-78.0) years old, and 63.2% were male. The ratio of partial pressure of oxygen in arterial blood to the fractional of inspiratory oxygen concentration in COVID-19-induced ARDS was lower than that in influenza A induced ARDS during the initial stages of mechanical ventilation (influenza A induced ARDS 216.1 vs. COVID-19-induced ARDS 167.9, p = 0.009, day 1). The positive end expiratory pressure remained consistently higher in the COVID-19 group throughout the follow-up period (7.0 vs. 10.0, p < 0.001, day 1). COVID-19 and influenza A initially showed different directions for peak inspiratory pressure and dynamic compliance; however, after day 3, both groups exhibited similar directions. Dynamic driving pressure exhibited opposite trends between the two groups during mechanical ventilation. CONCLUSIONS: Respiratory mechanics show clear differences between COVID-19-induced ARDS and influenza A induced ARDS. Based on these findings, we can consider future treatment strategies for COVID-19-induced ARDS.

Risk Factors for Unfavorable Outcomes of Tuberculosis in Korea: Implications for Patient-Centered Care in Tuberculosis Treatment.

BACKGROUND: The treatment success rate for tuberculosis (TB) has stagnated at 80-81% in South Korea, indicating unsatisfactory outcomes. Enhancing treatment success rate necessitates the development of individualized treatment approaches for each patient. This study aimed to identify the risk factors associated with unfavorable treatment outcomes to facilitate tailored TB care. METHODS: We retrospectively analyzed the data of patients with active TB between January 2019 and December 2020 at a single tertiary referral center. We classified unfavorable treatment outcomes according to the 2021 World Health Organization guidelines as follows: "lost to follow-up" (LTFU), "not evaluated" (NE), "death," and "treatment failure" (TF). Moreover, we analyzed risk factors for each unfavorable outcome using Cox proportional hazard regression analysis. RESULTS: A total of 659 patients (median age 62 years; male 54.3%) were included in the study. The total unfavorable outcomes were 28.1%: 4.6% LTFU, 9.6% NE, 9.1% deaths, and 4.9% TF. Multivariate analysis showed that a culture-confirmed diagnosis of TB was associated with a lower risk of LTFU (adjusted hazard ratio [aHR], 0.25; 95% confidence interval [CI], 0.10-0.63), whereas the occurrence of adverse drug reactions (ADRs) significantly increased the risk of LTFU (aHR, 6.63; 95% CI, 2.63-16.69). Patients living far from the hospital (aHR, 4.47; 95% CI, 2.50-7.97) and those with chronic kidney disease (aHR, 3.21; 95% CI, 1.33-7.75) were at higher risk of being transferred out to other health institutions (NE). Higher mortality was associated with older age (aHR, 1.06; 95% CI, 1.04-1.09) and comorbidities. The ADRs that occurred during TB treatment were a risk factor for TF (aHR, 6.88; 95% CI, 2.24-21.13). CONCLUSION: Unfavorable outcomes of patients with TB were substantial at a tertiary referral center, and the risk factors for each unfavorable outcome varied. To improve treatment outcomes, close monitoring and the provision of tailored care for patients with TB are necessary.

Pulmonary Rehabilitation Is Associated With Decreased Exacerbation and Mortality in Patients With COPD: A Nationwide Korean Study.

BACKGROUND: Poor uptake to pulmonary rehabilitation (PR) is still challenging around the world. There have been few nationwide studies investigating whether PR impacts patient outcomes in COPD. We investigated the change of annual PR implementation rate, medical costs, and COPD outcomes including exacerbation rates and mortality between 2015 and 2019. RESEARCH QUESTION: Does PR implementation improve outcomes in patients with COPD in terms of direct cost, exacerbation, and mortality? STUDY DESIGN AND METHODS: Data of patients with COPD extracted from a large Korean Health Insurance Review and Assessment service database (2015-2019) were analyzed to determine the trends of annual PR implementation rate and direct medical costs of PR. Comparison of COPD exacerbation rates between pre-PR and post-PR, and the time to first exacerbation and mortality rate according to PR implementation, were also assessed. RESULTS: Among all patients with COPD in South Korea, only 1.43% received PR. However, the annual PR implementation rate gradually increased from 0.03% to 1.4% during 4 years, especially after health insurance coverage commencement. The direct medical cost was significantly higher in the PR group than the non-PR group, but the costs in these groups showed decreasing and increasing trends, respectively. Both the incidence rate and frequency of moderate-to-severe and severe exacerbations were lower during the post-PR period compared with the pre-PR period. The time to the first moderate-to-severe and severe exacerbations was longer in the PR group than the non-PR group. Finally, PR implementation was associated with a significant decrease in mortality. INTERPRETATION: We concluded that health insurance coverage increases PR implementation rates. Moreover, PR contributes toward improving outcomes including reducing exacerbation and mortality in patients with COPD. However, despite the well-established benefits of PR, its implementation rate remains suboptimal.

Impact of age on mortality and transfer to long-term care in patients in an intensive care unit.

BACKGROUND: In the global trend of population aging, age is one of the significant factors to be considered in critically ill patients. However, the impact of age on clinical outcomes and long-term prognosis in this population varies across different studies. METHODS: We conducted a retrospective cohort analysis for patients admitted to the medical intensive care unit (ICU) (30 beds) between January 2017 and December 2020 at the tertiary referral hospital in Korea. Patients were classified into three groups according to age: <65 years, old age (65-79 years), and very old age (≥ 80 years). Subsequently, enrolled patients were analyzed for acute mortality and long-term prognosis. RESULTS: Among the 1584 patients, the median age was 67.0 (57.0-76.0) years, and 65.2% were male. Median ICU length of stay (LOS) (8, 9, and 10 days in < 65, 65-79, and ≥ 80 years, respectively; p = 0.006) and the proportion of patients who were transferred to long-term care hospital at the time of discharge (12.9% vs. 28.3% vs. 39.4%, respectively; p < 0.001) increased with age. Multivariable logistic analysis showed no significant difference in the 28-day mortality in the old age (adjusted odds ratio [aOR] 0.88; 95% confidence interval [CI] 0.65-1.17) and very old age (aOR 1.05; 95% CI 0.71-1.55) groups compared to that in patients with age < 65 years. However, the relevance of the proportion of ICU LOS ≥ 7 days and transfers to other hospitals after discharge increased with age. CONCLUSIONS: Age did not affect acute mortality in critical illness patients. However, surviving older age groups required more long-term care facilities compared to patients younger than 65 years after acute management. These results indicate that in an aging society, the importance of not only acute management but also long-term care facilities may increase for critical illness patients.

Characteristics and risk factors of mortality in patients with systemic sclerosis-associated interstitial lung disease.

BACKGROUND: Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by dysregulation of fibroblast function, which often involves the lungs. Interstitial lung disease (ILD) associated with SSc (SSc-ILD) is a major cause of death among patients with SSc. Our study aimed to identify risk factors for mortality and compare the clinical characteristics of patients with SSc-ILD. PATIENTS AND METHODS: Patients were retrospectively enrolled between 2010 and 2018 in a tertiary hospital in Korea. Patients with SSc-ILD were classified depending on the first pulmonary function test or radiologic findings: extensive (n = 46, >20% disease extent on computed tomography (CT) or forced vital capacity [FVC] < 70% in indeterminate cases) and limited (n = 60, <20% disease extent on CT or FVC ≥70% in indeterminate cases). RESULTS: Patients in the extensive group were younger (mean age ± SD 49.3 ± 11.5) than those in the limited group (53.9 ± 12.5, p = .067) at diagnosis. The extensive group showed frequent pulmonary hypertension (43.5% vs. 16.7%, p = .009) and higher erythrocyte sedimentation rate (61.3 ± 33.7 vs. 42.1 ± 26.0, p = .003) and mortality (32.6%, mean duration of follow-up, 100.0 ± 44.7 months vs. 10.0%, 86.0 ± 53.4 months, p = .011). ILD was detected within five years from the first visit (median years 3.5 (1.0, 6.0) vs. 4.5 (0.6, 9.0), survivors vs. non-survivors), and mortality occurred in 19.8% of all patients during a 15-year follow-up. Older age, lower FVC, and initial disease stage (limited or extensive) were associated with mortality, but FVC decline was similar in the limited and extensive groups, such as 15-20% in the first year and 8-10% in the next year, regardless of the initial extent of the disease. CONCLUSIONS: Approximately 10% of patients with SSc-ILD in the limited and extensive group showed progression. ILD was detected at a median of less than five years from the first visit; therefore, it is necessary to carefully monitor patients' symptoms and signs from an early stage. Long-term surveillance is also required.Key messagesPatients with systemic sclerosis-interstitial lung disease manifested a heterogeneous disease course.Approximately 10% of the patients in the limited group showed progression, which was similar to the proportion of patients in the extensive group.Interstitial lung disease was detected at a median of less than five years from the first visit.

Longitudinal association between adiposity changes and lung function deterioration.

BACKGROUND: The longitudinal relationship between adiposity and lung function is controversial. We aimed to investigate the long-term association between adiposity changes and lung function in a middle-aged general Asian population. METHODS: In total, 5011 participants (average age, 54 years; 45% men) were enrolled from a community-based prospective cohort. During the follow-up period (median 8 years), both spirometry and bio-electrical impedance analysis were performed biannually. Individual slopes of the fat mass index (FMI; fat mass divided by the square of height in meters) and waist-to-hip ratio (WHR) were calculated using linear regression analysis. Multivariate linear mixed regression analysis was used to determine the long-term association between adiposity changes and lung function. RESULTS: The FMI was inversely associated with forced vital capacity (FVC) (estimated: - 31.8 mL in men, - 27.8 mL in women) and forced expiratory volume in 1 s (FEV1) (estimated: - 38.2 mL in men, - 17.8 mL in women) after adjusting for baseline age, height, residential area, smoking exposure (pack-years, men only), initial adiposity indices, and baseline lung function. The WHR was also inversely associated with FVC (estimated = - 1242.2 mL) and FEV1 (estimated = - 849.8 mL) in men. The WHR-increased group showed a more rapid decline in lung function than the WHR-decreased group in both the fat-gain and fat-loss groups. CONCLUSION: Adiposity was associated with the long-term impairment of lung function. Central obesity was the main driver of lung function impairment in the middle-aged general Asian population, regardless of fat mass changes.

Identification of Biomarkers for the Diagnosis of Sepsis-Associated Acute Kidney Injury and Prediction of Renal Recovery in the Intensive Care Unit.

PURPOSE: Acute kidney injury (AKI) following sepsis is associated with higher mortality; however, reliable biomarkers for AKI development and recovery remain to be elucidated. MATERIALS AND METHODS: Patients with sepsis admitted to the medical intensive care unit (ICU) of Severance Hospital between June 2018 and May 2019 were prospectively analyzed. Patients were divided into those with and without AKI within 48 hours. Patients with septic AKI were subdivided into AKI-recovery and non-recovery groups based on whether their kidney injury recovered within 7 days. RESULTS: A total of 84 patients were enrolled. The baseline creatinine (2.9 mg/dL vs. 0.8 mg/dL vs. 1.2 mg/dL, p<0.001), Charlson Comorbidity Index (4.5 vs. 2.0 vs. 3.0, p=0.002), Sequential Organ Failure Assessment (10.0 vs. 6.5 vs. 8.0, p<0.001), and Acute Physiology and Chronic Health Evaluation II scores (32.0 vs. 21.5 vs. 30.5, p=0.004) were higher in the non-recovery AKI group compared to the non-AKI and AKI-recovery groups. The Kaplan-Meier curves revealed that non-recovery from AKI was associated with lower survival (p<0.001). High-lactate (p≤0.05) and kynurenine levels (p≤0.05) were associated with non-recovery of renal function following AKI. The areas under the curve for predicting non-recovery from AKI were 0.693 and 0.721 for lactate and kynurenine, respectively. The survival rate was lower in the high-kynurenine (p=0.040) and high-lactate (p=0.010) groups. CONCLUSION: The mortality of patients who recovered from AKI was comparable to that of patients without AKI. Lactate and kynurenine could be useful biomarkers for the diagnosis and recovery of AKI following sepsis.

Protective effect of methotrexate on lung function and mortality in rheumatoid arthritis-related interstitial lung disease: a retrospective cohort study.

BACKGROUND: Studies on the risk and protective factors for lung function decline and mortality in rheumatoid arthritis-related interstitial lung disease (RA-ILD) are limited. OBJECTIVES: We aimed to investigate clinical factors and medication uses associated with lung function decline and mortality in RA-ILD. METHODS: This retrospective cohort study examined the medical records of patients with RA-ILD who visited Severance Hospital between January 2006 and December 2019. We selected 170 patients with RA-ILD who had undergone at least one spirometry test and chest computed tomography scan. An absolute decline of ⩾10% in the functional vital capacity (FVC) was defined as significant decline in pulmonary function. Data for analysis were retrieved from electronic medical records. RESULTS: Ninety patients (52.9%) were female; the mean age was 64.0 ± 10.2 years. Multivariate logistic regression showed that a high erythrocyte sediment rate level at baseline [odds ratio (OR) = 3.056; 95% confidence interval (CI) = 1.183-7.890] and methotrexate (MTX) use (OR = 0.269; 95% CI = 0.094-0.769) were risk and protective factors for lung function decline, respectively. Multivariate Cox regression analysis indicated that age ⩾65 years (OR = 2.723; 95% CI = 1.142-6.491), radiologic pattern of usual interstitial pneumonia (UIP) or probable UIP (OR = 3.948; 95% CI = 1.522-10.242), baseline functional vital capacity (FVC) % predicted (OR = 0.971; 95% CI = 0.948-0.994), and MTX use (OR = 0.284; 95% CI = 0.091-0.880) were predictive of mortality. CONCLUSION: We identified risk and protective factors for lung function decline and mortality in patients with RA-ILD. MTX use was associated with favorable outcome in terms of both lung function and mortality in our cohort.

Sarcopenia is associated with cardiovascular risk in men with COPD, independent of adiposity.

BACKGROUND: Sarcopenia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD), but its relationship with chronic obstructive pulmonary disease (COPD) has not been fully determined. This study is aimed to investigate the association between sarcopenia and risk for ASCVD in patients with COPD, independent of central obesity and fat mass. METHODS: Data regarding 704 men with COPD (mean age: 63.4 years) were extracted from the 2008 to 2011 Korean National Health and Nutrition Examination Surveys. Sarcopenia index and fat mass were assessed using dual-energy X-ray absorptiometry. Sarcopenia was defined according to the presence of sarcopenia index values < 1 standard deviation from the cutoff (0.774) among the study participants. ASCVD risk was evaluated using American College of Cardiology/American Heart Association guidelines. High probability of ASCVD was defined as ASCVD risk > 20%. RESULTS: The quartile-stratified sarcopenia index was negatively associated with ASCVD risk (P < 0.001). ASCVD risk and prevalence of high ASCVD risk were significantly greater in sarcopenic participants than in non-sarcopenic participants, regardless of central obesity and fat mass (all P < 0.001). Multivariate regression analyses demonstrated an independent association between sarcopenia and ASCVD risk (estimated ± standard error = 3.63 ± 0.77%, P < 0.001) and high ASCVD risk (odds ratio [OR] = 2.32, 95% confidence interval [CI] 1.05-5.15, P = 0.039). Furthermore, sarcopenia was an independent factor for high ASCVD risk in participants with moderate to very severe airflow limitation (OR = 2.97, 95% CI 1.06-8.36, P < 0.001). CONCLUSIONS: Sarcopenia was significantly associated with an increased risk for ASCVD in men with COPD, independent of central obesity and fat mass. High ASCVD risk was significantly associated with sarcopenia, particularly in participants with moderate to very severe airflow limitation.

Lysophosphatidylcholine Alleviates Acute Lung Injury by Regulating Neutrophil Motility and Neutrophil Extracellular Trap Formation.

Sepsis is predominantly initiated by bacterial infection and can cause systemic inflammation, which frequently leads to rapid death of the patient. However, this acute systemic inflammatory response requires further investigation from the perspectives of clinical judgment criteria and early treatment strategies for the relief of symptoms. Lysophosphatidylcholine (LPC) 18:0 may relieve septic symptoms, but the relevant mechanism is not clearly understood. Therefore, we aimed to assess the effectiveness of LPC as a therapeutic treatment for acute inflammation in the lung induced by lipopolysaccharide in mice. Systemic inflammation of mice was induced by lipopolysaccharide (LPS) inoculation to investigate the role of LPC in the migration and the immune response of neutrophils during acute lung injury. By employing two-photon intravital imaging of the LPS-stimulated LysM-GFP mice and other in vitro and in vivo assays, we examined whether LPC alleviates the inflammatory effect of sepsis. We also tested the effect of LPC to human neutrophils from healthy control and sepsis patients. Our data showed that LPC treatment reduced the infiltration of innate immune cells into the lung. Specifically, LPC altered neutrophil migratory patterns and enhanced phagocytic efficacy in the damaged lung. Moreover, LPC treatment reduced the release of neutrophil extracellular trap (NET), which can damage tissue in the inflamed organ and exacerbate disease. It also reduced human neutrophil migration under inflammatory environment. Our results suggest that LPC can alleviate sepsis-induced lung inflammation by regulating the function of neutrophils. These findings provide evidence for the beneficial application of LPC treatment as a potential therapeutic strategy for sepsis.

Complications related to extracorporeal membrane oxygenation support as a bridge to lung transplantation and their clinical significance.

BACKGROUND: Incidence of complications related extracorporeal membrane oxygenation (ECMO) support as a bridge to lung transplantation (BTT) and its association with the patient outcome in lung transplantation (LT) has not been well documented in previous studies. OBJECTIVES: We evaluated the incidence of complications related to the use of ECMO support as a BTT, and the association between the occurrence of the complications and patient outcomes in LTs. METHODS: This retrospective cohort study investigated 100 consecutive patients who started ECMO support as a BTT between April 2013 and March 2020. Data for the analyses were retrieved from electronic medical records. RESULTS: Fifty-six percent of the patients experienced at least one complication during the BTT with ECMO. Major bleeding was the most common complication. In multivariate logistic regression analysis, occurrence of oxygenator thromboses (OR 16.438, P = 0.008) and the use of renal replacement therapy (RRT) (OR 32.288, P < 0.001) were associated with a failed BTT. In the subgroup analysis of the LT recipients, intracranial hemorrhages, (OR 13.825, P = 0.021), RRT use, (OR 11.395, P = 0.038), and bloodstream infection occurrence (OR 6.210; P = 0.034) were identified as risk factors for in-hospital mortality. CONCLUSIONS: The occurrence of complications during the use of ECMO support as a BTT was associated with unfavorable outcomes in LTs. Close monitoring and the proper management of these complications may be important to achieve better outcomes in patients using ECMO support as a BTT.

Long-term clinical course and progression of lymphangioleiomyomatosis in a single lung transplant referral centre in Korea.

We aimed to describe the clinical features of lymphangioleiomyomatosis (LAM) in Korean patients and identify factors associated with progressive disease (PD). Clinical features of 54 patients with definite or probable LAM from 2005 to 2018 were retrospectively analysed. Common features were pneumothorax (66.7%) and abdominal lymphadenopathy (50.0%). Twenty-three (42.6%) patients were initially treated with mechanistic target of rapamycin (mTOR) inhibitors. Lung transplantation (LT) was performed in 13 (24.1%) patients. Grouped based on the annual decline in forced expiratory volume in 1 s (FEV1) from baseline and LT, 36 (66.7%) patients exhibited stable disease (SD). All six deaths (11.1%) occurred in PD. Proportion of SD was higher in those treated initially with mTOR inhibitors than in those under observation (p = 0.043). Univariate analysis revealed sirolimus use, and baseline forced vital capacity, FEV1, and diffusing capacity of the lungs for carbon monoxide are associated with PD. Multivariate analysis showed that only sirolimus use (odds ratio 0.141, 95% confidence interval 0.021-0.949, p = 0.044) reduced PD. Kaplan-Meier analysis estimates overall survival of 92.0% and 74.7% at 5 and 10 years, respectively. A considerable proportion of LAM patients remain clinically stable without treatment. LT is an increasingly viable option for patients with severe lung function decline.

NADPH oxidase 4 signaling in a ventilator-induced lung injury mouse model.

BACKGROUND: For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. In this study, we investigated the role of NOX4 using NOX4 knockout (KO) mice and NOX4 inhibitors in a ventilator-induced lung injury (VILI) model. METHODS: Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV ± DMSO; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor. In the VILI model, the supine position was maintained at 24 mL/kg volume, 0 cm H2O PEEP, 100/min respiratory rate, and 0.21 inspired oxygen fraction. In the NOX4 inhibitor group, 50 µL anti-GKT 137831 inhibitor was injected intraperitoneally, 2 h after ventilator use. After 5 h of HTV, mice in the ventilator group were euthanized, and their lung tissues were obtained for further analysis. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 and EphA2 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined. RESULTS: Cell counts from BALFs were significantly lower in the NOX4 KO with HTV group (p < 0.01) and EphA2 KO with HTV group (p < 0.001) compared to that in the HTV group. In the NOX4 inhibitor group, cell counts and protein concentrations from BALF were significantly lower than those in the HTV group (both, p < 0.001). In the NOX4 KO group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (p < 0.001). In patients with respiratory disease, NOX4 and EphA2 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the intensive care unit. CONCLUSION: In the VILI model with high tidal volume, NOX4 KO, EphA2 KO or monoclonal antibodies attenuated the VILI. NOX4 and EphA2 levels were significantly higher in patients with pneumonia and especially in mechanical ventilated in the ICU. Inhibition of Nox4 is a potential therapeutic target for the prevention and reduction of VILI.

Reference values of skeletal muscle area for diagnosis of sarcopenia using chest computed tomography in Asian general population.

BACKGROUND: Diagnostic cutoff points for sarcopenia in chest computed tomography (CT) have not been established although CT is widely used for investigating skeletal muscles. This study aimed to determine reference values for sarcopenia of thoracic skeletal muscles acquired from chest CT scans and to analyse variables related to sarcopenia using the cutoff values determined in a general Asian population. METHODS: We retrospectively reviewed chest CT scans of 4470 participants (mean age 54.8 ± 9.9 years, 65.8% male) performed at a check-up centre in South Korea (January 2016-August 2017). To determine cutoffs, 335 participants aged 19-39 years (mean age 35.2 ± 3.6 years, 75.2% male) were selected as the healthy and younger reference group, and 4135 participants aged ≥40 years (mean age 56.4 ± 8.4 years, 65.1% male) were selected as the study group. We measured the following: cross-sectional area (CSA) of the pectoralis, intercostalis, paraspinal, serratus, and latissimus muscles at the 4th vertebral region (T4CSA ); T4CSA divided by height2 (T4MI); pectoralis muscle area (PMCSA ); and PMCSA divided by height2 (PMI) at the 4th vertebral region. Sarcopenia cutoff was defined as sex-specific values of less than -2 SD below the mean from the reference group. RESULTS: In the reference group, T4CSA , T4MI, PMCSA , and PMI cutoffs for sarcopenia were 100.06cm2 , 33.69cm2 /m2 , 29.00cm2 , and 10.17cm2 /m2 in male, and 66.93cm2 , 26.01cm2 /m2 , 18.29cm2 , and 7.31cm2 /m2 in female, respectively. The prevalence of sarcopenia in the study group measured with T4CSA , T4MI, PMCSA and PMI cutoffs were 11.4%, 8.7%, 8.5%, and 10.1%, respectively. Correlations were observed between appendicular skeletal mass divided by height2 measured by bioelectrical impedance analysis (BIA) and T4CSA (r = 0.82; P < 0.001)/T4MI (r = 0.68; P < 0.001), and ASM/height2 measured by BIA and PMCSA (r = 0.72; P < 0.001)/PMI (r = 0.63; P < 0.001). In the multivariate logistic regression models, sarcopenia defined by T4CSA /T4MI were related to age [odds ratio (95% confidence interval), P-values: 1.09 (1.07-1.11), <0.001/1.05 (1.04-1.07), <0.001] and diabetes [1.60 (1.14-2.25), 0.007/1.47 (1.01-2.14), 0.043]. Sarcopenia defined by PMCSA /PMI were related to age [1.09 (1.08-1.10), <0.001/1.05 (1.03-1.06), <0.001], male sex [0.23 (0.18-0.30), <0.001/0.47 (0.32-0.71), <0.001], diabetes [2.30 (1.73-3.05), <0.001/1.63 (1.15-2.32), 0.007], history of cancer [2.51 (1.78-3.55), <0.001/1.61 (1.04-2.48), 0.033], and sufficient physical activity [0.67 (0.50-0.89), 0.007/0.74 (0.56-0.99), 0.042]. CONCLUSIONS: The reference cutoff values of a general population reported here will enable sex-specific standardization of thoracic muscle mass quantification and sarcopenia assessment.

Clinical impact of pneumothorax in patients with Pneumocystis jirovecii pneumonia and respiratory failure in an HIV-negative cohort.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) with acute respiratory failure can result in development of pneumothorax during treatment. This study aimed to identify the incidence and related factors of pneumothorax in patients with PCP and acute respiratory failure and to analyze their prognosis. METHODS: We retrospectively reviewed the occurrence of pneumothorax, including clinical characteristics and results of other examinations, in 119 non-human immunodeficiency virus patients with PCP and respiratory failure requiring mechanical ventilator treatment in a medical intensive care unit (ICU) at a tertiary-care center between July 2016 and April 2019. RESULTS: During follow up duration, twenty-two patients (18.5%) developed pneumothorax during ventilator treatment, with 45 (37.8%) eventually requiring a tracheostomy due to weaning failure. Cytomegalovirus co-infection (odds ratio 13.9; p = 0.013) was related with occurrence of pneumothorax in multivariate analysis. And development of pneumothorax was not associated with need for tracheostomy and mortality. Furthermore, analysis of survivor after 28 days in ICU, patients without pneumothorax were significantly more successful in weaning from mechanical ventilator than the patients with pneumothorax (44% vs. 13.3%, p = 0.037). PCP patients without pneumothorax showed successful home discharges compared to those who without pneumothorax (p = 0.010). CONCLUSIONS: The development of pneumothorax increased in PCP patient with cytomegalovirus co-infection, pneumothorax might have difficulty in and prolonged weaning from mechanical ventilators, which clinicians should be aware of when planning treatment for such patients.