Search

Backgroud: This prospective randomized trial evaluated the clinical efficacy of inhaled colistin administered through two distinct nebulizer types, a vibrating mesh nebulizer (VMN) and a jet nebulizer (JN), in the treatment of ventilator-associated pneumonia caused by multidrug-resistant bacteria. In addition, an in vitro model was used to determine the optimal delivery of colistin. Method: Thirty-two patients prescribed intravenous (IV) colistin inhalation were randomized to receive either a VMN (n = 17) or a JN (n = 15), then compared to the control group (IV alone) over a 7-to 10-day period. The primary endpoint was the clinical pulmonary infection score (CPIS), and the secondary endpoints were the Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACE) score, and duration of ventilator use. Results: Results from in vitro testing demonstrated that VMN delivered a significantly higher colistin dose than JN (35.68 ± 3.55% vs. 23.56 ± 3.31%; p < 0.001) when positioned at the humidifier inlet. Compared to the IV alone group, the IV with inhalation group yielded significant improvements in CPIS, SOFA score, and APACHE score on day 7; nevertheless, clinical outcomes between the two nebulizers were statistically indistinguishable. Conclusions: In conclusion, although VMN delivers a higher dose in vitro, both nebulizers yielded comparable clinical outcomes. This study was registered at US Clinical Trial Registration (NCT04633317).

Abstract Background/Objective Bereaved family surrogates from intensive care units (ICU) are at risk of comorbid anxiety, depression, and post-traumatic stress disorder (PTSD), but the temporal reciprocal relationships among them have only been examined once among veterans. This study aimed to longitudinally investigate these never-before-examined temporal reciprocal relationships for ICU family members over their first two bereavement years. Methods In this prospective, longitudinal, observational study, symptoms of anxiety, depression, and PTSD were assessed among 321 family surrogates of ICU decedents from 2 academically affiliated hospitals in Taiwan by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale, and the Impact of Event Scale-Revised, respectively at 1, 3, 6, 13, 18, and 24 months postloss. Cross-lagged panel modeling was conducted to longitudinally examine the temporal reciprocal relationships among anxiety, depression, and PTSD. Results Examined psychological-distress levels were markedly stable over the first 2 bereavement years: autoregressive coefficients for symptoms of anxiety, depression, and PTSD were 0.585–0.770, 0.546–0.780, and 0.440–0.780, respectively. Cross-lag coefficients showed depressive symptoms predicted PTSD symptoms in the first bereavement year, whereas PTSD symptoms predicted depressive symptoms in the second bereavement year. Anxiety symptoms predicted symptoms of depression and PTSD at 13 and 24 months postloss, whereas depressive symptoms predicted anxiety symptoms at 3 and 6 months postloss while PTSD symptoms predicted anxiety symptoms during the second bereavement year. Conclusions Different patterns of temporal relationships among symptoms of anxiety, depression, and PTSD over the first 2 bereavement years present important opportunities to target symptoms of specific psychological distress at different points during bereavement to prevent the onset, exacerbation, or maintenance of subsequent psychological distress.

Abstract Smoking rates in the military are evaluated through questionnaire surveying. Because the accurate identification of smokers facilitates the provision of smoking cessation services, this study conducted urine cotinine concentration testing to verify the accuracy of self-reported smoking behavior by female volunteer soldiers and analyzed the effects of second-hand smoking on urine cotinine concentrations. This study is a cross-sectional study conducted using purposive sampling on female volunteer soldiers receiving training at the Taichung Recruit Training Center in May 2014. This study simultaneously collected questionnaires and urine samples, and urine samples were analyzed with an enzyme-linked immunosorbent assay. The self-reported smoking rate of female volunteer soldiers was 19.3%, whereas the smoking rate as determined by urine cotinine concentration testing was 26.3%, indicating an overall underestimation of 7.0%. Chi-square (χ2) goodness of fit test results indicated that the distribution of self-reported smoking behaviors and that verified from urine cotinine concentration testing were significantly different. The sensitivity of self-reported smoking behavior was 66.7% with a specificity of 97.6%. There was no significant association between second-hand smoking and urine cotinine concentrations. Questionnaire survey self-reporting methods could underestimate the smoking behavior of female volunteer soldiers and routine testing with biochemical verification is necessary.

Abstract Background Bereaved ICU family surrogates are at risk of comorbid prolonged grief disorder (PGD), posttraumatic stress disorder (PTSD), and depression. Knowledge about temporal relationships between PGD, PTSD, and depression is limited by a lack of relevant studies and diverse or inappropriate assessment time frames given the duration criterion for PGD. We aimed to determine the temporal reciprocal relationships between PGD, PTSD, and depressive symptoms among ICU decedents’ family surrogates during their first 2 bereavement years with an assessment time frame reflecting the PGD duration criterion. Methods This prospective, longitudinal, observational study examined PGD, PTSD, and depressive symptoms among 303 family surrogates of ICU decedents from two academic hospitals using 11 items of the Prolonged Grief Disorder-13, the Impact of Event Scale—Revised, and the depression subscale of the Hospital Anxiety and Depression Scale, respectively, at 6, 13, 18, and 24 months post-loss. Cross-lagged panel modeling was conducted: autoregressive coefficients indicate variable stability, and cross-lagged coefficients indicate the strength of reciprocal relationships among variables between time points. Results Symptoms (autoregressive coefficients) of PGD (0.570–0.673), PTSD (0.375–0.687), and depression (0.591–0.655) were stable over time. Cross-lagged standardized coefficients showed that depressive symptoms measured at 6 months post-loss predicted subsequent symptoms of PGD (0.146) and PTSD (0.208) at 13 months post-loss. PGD symptoms did not predict depressive symptoms. PTSD symptoms predicted subsequent depressive symptoms in the second bereavement year (0.175–0.278). PGD symptoms consistently predicted subsequent PTSD symptoms in the first 2 bereavement years (0.180–0.263), whereas PTSD symptoms predicted subsequent PGD symptoms in the second bereavement year only (0.190–0.214). PGD and PTSD symptoms are bidirectionally related in the second bereavement year. Conclusions PGD, PTSD, and depressive symptoms can persist for 2 bereavement years. Higher PGD symptoms at 6 months post-loss contributed to the exacerbation of PTSD symptoms over time, whereas long-lasting PTSD symptoms were associated with prolonged depression and PGD symptoms beyond the first bereavement year. Identification and alleviation of depression and PGD symptoms as early as 6 months post-loss enables bereaved surrogates to grieve effectively and avoid the evolution of those symptoms into long-lasting PGD, PTSD, and depression.

Abstract Background/objective Bereaved ICU family surrogates’ psychological distress, e.g., anxiety, depression, and post-traumatic stress disorder (PTSD), is usually examined independently, despite the well-recognized comorbidity of these symptoms. Furthermore, the few studies exploring impact of psychological distress on development of prolonged grief disorder (PGD) did not consider the dynamic impact of symptom evolution. We identified surrogates’ distinct patterns/states of comorbid psychological distress and their evolution over the first 3 months of bereavement and evaluated their associations with PGD at 6-month postloss. Methods A longitudinal observational study was conducted on 319 bereaved surrogates. Symptoms of anxiety, depression, PTSD, and PGD were measured by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised scale, and the PGD-13, respectively. Distinct psychological-distress states and their evolution were examined by latent transition analysis. Association between psychological-distress states and PGD symptoms was examined by logistic regression. Results Three distinct comorbid psychological-distress states (prevalence) were initially identified: no distress (56.3%), severe-depressive/borderline-anxiety distress (30.5%), and severe-anxiety/depressive/PTSD distress (13.3%). Except for those in the stable no-distress state, surrogates tended to regress to states of less psychological distress at the subsequent assessment. The proportion of participants in each psychological-distress state changed to no distress (76.8%), severe-depressive/borderline-anxiety distress (18.6%), and severe-anxiety/depressive/PTSD distress (4.6%) at 3-month postloss. Surrogates in the severe-depressive/borderline-anxiety distress and severe-anxiety/depressive/PTSD-distress state at 3-month postloss were more likely to develop PGD at 6-month postloss (OR [95%] = 14.58 [1.48, 143.54] and 104.50 [10.45, 1044.66], respectively). Conclusions A minority of family surrogates of ICU decedents suffered comorbid severe-depressive/borderline-anxiety distress and severe-anxiety/depressive/PTSD symptoms during early bereavement, but they were more likely to progress into PGD at 6-month postloss.

Background: Ventilation limitation has a significant adverse effects on cardiovascular function and tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease (COPD). High flow nasal cannula (HFNC) improve ventilation by washing out the anatomical dead space and providing oxygen at constant concentration. This study aimed to examine the effects of HFNC on the exercise performance and hemodynamic status in COPD patients. Methods: Fifteen patients with COPD performed two constant load exercise tests (CLET) at the 70% of maximum workload achieved at a previous incremental exercise test on arm ergometer. The CLET were performed with HFNC and with nasal cannula (NC) in random order. The hemodynamics parameters of subjects during exercises were measured by a bioelectrical impedance device. The tissue oxygenation status (oxygenated hemoglobin, deoxygenated hemoglobin (hHb), total hemoglobin) was measured by a near infrared spectrophotometer. Results: The exercise duration was longer for HFNC test than NC test (962.9 ± 281.7 s, vs 823.9 ± 184.9 s, p < 0.05). At the end of CLET, the PetCO2 was lower for HFNC than NC (29.3 ± 5.1 mmHg vs 32.1 ± 5.5 mmHg, p 0.05), stroke volume (NC:73.5 ± 21.0 vs HFNC 67.5 ± 16.3 ml, p > 0.05). The changes of hHb in muscle tissues was significantly lower in HFNC test than that in NC test (p

PURPOSE: Muscle atrophy and diaphragm dysfunction are common with prolonged mechanical ventilation (PMV). Electrical stimulation on peripheral muscles has been shown to be beneficial in the improvement of muscle function. This study examined the effects of transcutaneous electrical diaphragmatic stimulation (TEDS) on respiratory muscle strength and weaning outcomes in patients with PMV. METHODS: Participants on ventilation for ≥21 days were randomly assigned to TEDS (n = 29) and control (n = 30) groups. The TEDS group received muscle electrical stimulation for 30 min/session/day throughout the intervention. Pulmonary function parameters (tidal volume, respiratory rate, and rapid shallow breathing index), and respiratory muscle strength (Pimax, Pemax) were assessed. The hospitalization outcome, including weaning rate and length of stay, was followed up until discharge. RESULTS: After TEDS, there was a significant increase in Pemax (10 [8–20] vs. 20 [10–22] cmH2O, P = 0.034) in the intervention group. At the end of the study, the improvement of minute volume in the TEDS group (0.64 (−0.67) was significantly higher than the control group (−0.64 (−2.5–0.78) (P = 0.008). In the control group, there was no significant difference between pre- and post-measurement of weaning parameters. There was a significant difference between groups in the weaning rate, with a higher rate in the TEDS group (90%) when compared with that in the control group (66.7%) (P =0.021). CONCLUSION: TEDS was significantly associated with increased respiratory muscle strength in patients with PMV. TEDS may be useful to facilitate weaning in this population.

Abstract Background/Objective Death in intensive care units (ICUs) may increase bereaved family members’ risk for posttraumatic stress disorder (PTSD). However, posttraumatic stress-related symptoms (hereafter as PTSD symptoms) and their precipitating factors were seldom examined among bereaved family members and primarily focused on associations between PTSD symptoms and patient/family characteristics. We aimed to investigate the course and predictors of clinically significant PTSD symptoms among family members of deceased ICU patients by focusing on modifiable quality indicators for end-of-life ICU care. Method In this longitudinal observational study, 319 family members of deceased ICU patients were consecutively recruited from medical ICUs from two Taiwanese medical centers. PTSD symptoms were assessed at 1, 3, 6, and 13 months post-loss using the Impact of Event Scale-Revised (IES-R). Family satisfaction with end-of-life care in ICUs was assessed at 1 month post-loss. End-of-life care received in ICUs was documented over the patient’s ICU stay. Predictors for developing clinically significant PTSD symptoms (IES-R score ≥ 33) were identified by multivariate logistic regression with generalized estimating equation modeling. Results The prevalence of clinically significant PTSD symptoms decreased significantly over time (from 11.0% at 1 month to 1.6% at 13 months post-loss). Longer ICU stays (adjusted odds ratio [95% confidence interval] = 1.036 [1.006, 1.066]), financial insufficiency (3.166 [1.159, 8.647]), and reported use of pain medications (3.408 [1.230, 9.441]) by family members were associated with a higher likelihood of clinically significant PTSD symptoms among family members during bereavement. Stronger perceived social support (0.937 [0.911, 0.965]) and having a Do-Not-Resuscitate (DNR) order issued before the patient’s death (0.073 [0.011, 0.490]) were associated with a lower likelihood of clinically significant PTSD symptoms. No significant association was observed for family members’ satisfaction with end-of-life care (0.988 [0.944, 1.034]) or decision-making in ICUs (0.980 [0.944, 1.018]). Conclusions The likelihood of clinically significant PTSD symptoms among family members decreased significantly over the first bereavement year and was lower when a DNR order was issued before death. Enhancing social support and facilitating a DNR order may reduce the trauma of ICU death of a beloved for family members at risk for developing clinically significant PTSD symptoms.

Atrial fibrosis is an essential contributor to atrial fibrillation (AF). It remains unclear whether atrial endocardial endothelial cells (AEECs) that undergo endothelial-mesenchymal transition (EndMT) are among the sources of atrial fibroblasts. We studied human atria, TGF-β–treated human AEECs, cardiac-specific TGF-β–transgenic mice, and heart failure rabbits to identify the underlying mechanism of EndMT in atrial fibrosis. Using isolated AEECs, we found that miR-181b was induced in TGF-β–treated AEECs, which decreased semaphorin 3A (Sema3A) and increased EndMT markers, and these effects could be reversed by a miR-181b antagomir. Experiments in which Sema3A was increased by a peptide or decreased by a siRNA in AEECs revealed a mechanistic link between Sema3A and LIM-kinase 1/phosphorylated cofilin (LIMK/p-cofilin) signaling and suggested that Sema3A is upstream of LIMK in regulating actin remodeling through p-cofilin. Administration of the miR-181b antagomir or recombinant Sema3A to TGF-β–transgenic mice evoked increased Sema3A, reduced EndMT markers, and significantly decreased atrial fibrosis and AF vulnerability. Our study provides a mechanistic link between the induction of EndMT by TGF-β via miR-181b/Sema3A/LIMK/p-cofilin signaling to atrial fibrosis. Blocking miR-181b and increasing Sema3A are potential strategies for AF therapeutic intervention.

Abstract The prediction accuracy of pulse pressure variation (PPV) for fluid responsiveness was suggested to be unreliable in low tidal volume (VT) ventilation. However, high PEEP can cause ARDS patients relatively hypovolemic and more fluid responsive. We hypothesized that high PEEP 15 cmH2O can offset the disadvantage of low VT and improve the predictive performance of PPV. We prospectively enrolled 27 hypovolemic ARDS patients ventilated with low VT 6 ml/kg and three levels of PEEP (5, 10, 15 cmH2O) randomly. Each stage lasted for at least 5 min to allow for equilibration of hemodynamics and pulmonary mechanics. Then, fluid expansion was given with 500 ml hydroxyethyl starch (Voluven 130/70). The hemodynamics and PPV were automatically measured with a PiCCO2 monitor. The PPV values were significantly higher during PEEP15 than those during PEEP5 and PEEP10. PPV during PEEP15 precisely predicts fluid responsiveness with a cutoff value 8.8% and AUC (area under the ROC curve) of ROC (receiver operating characteristic curve) 0.847, higher than the AUC during PEEP5 (0.81) and PEEP10 (0.668). Normalizing PPV with driving pressure (PPV/Driving-P) increased the AUC of PPV to 0.875 during PEEP15. In conclusions, high PEEP 15 cmH2O can counteract the drawback of low VT and preserve the predicting accuracy of PPV in ARDS patients.

Abstract Background Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO). Methods We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded. Results A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 [95% CI 1.214–4.314], p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 [95% CI 1.018–1.104], p = 0.005) or MP referenced to PBW (HR 1.004 [95% CI 1.002–1.007], p 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H2O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (≦ 0.53 J/min/ml/cm H2O) (63.6% vs. 29.7%, p

Background: The incidence of acute respiratory distress syndrome (ARDS) and the mortality rate of H1N1 influenza pneumonia are unclear. The aim of this study is to investigate the clinical features and outcomes of adult patients admitted to intensive care units (ICUs) with H1N1 pneumonia related ARDS. Methods: This retrospective study included patients with confirmed H1N1 influenza pneumonia admitted to the ICUs of a medical center between July 2009 and May 2014. We investigated the patients’ characteristics, clinical presentations, illness severities, and outcomes. Results: Sixty-six patients were confirmed to have H1N1 influenza pneumonia requiring mechanical ventilation. Fifty-four of those patients (82%) developed ARDS, while their hospital mortality rate was 33% (22/66). There were no significant differences in the ICU and hospital mortality rates of the ARDS and non-ARDS patients. Among the ARDS patients, there were higher rates of solid malignant disease (22.8% vs. 2.8%, p = 0.038) and sepsis (66.7% vs. 33.3%, p = 0.020) and a higher mean tidal volume (8.9 ± 1.8 vs. 7.8 ± 1.9 ml/kg, p = 0.032) in the non-survivors than the survivors. Logistic regression analysis revealed that a high tidal volume (odds ratio = 1.448, 95 % CI = 1.033–2.030; p = 0.032) and sequential organ failure assessment (SOFA) score (odds ratio = 1.233, 95% CI = 1.029–1.478; p = 0.023) were the risk factors of hospital mortality. Conclusion: For H1N1 influenza pneumonia patients admitted to ICUs with mechanical ventilation, there is a high probability of developing ARDS with a modest mortality rate. For patients with ARDS due to H1N1 influenza pneumonia, the tidal volume and SOFA score are the predictors of hospital mortality. Keywords: ARDS, H1N1 influenza virus, Mortality, Pneumonia

Driving pressure (ΔP) and mechanical power (MP) are associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). We aimed to investigate which was better to predict mortality between changes in ΔP and MP. We reanalyzed data from a prospective observational cohort study of patients with ARDS in our hospital. Serial ΔP and MP values were calculated. The factors associated with survival were analyzed. Binary logistic regression showed that age (odds ratio (OR), 1.012; 95% confidence interval (CI), 1.003–1.022), Sequential Organ Failure assessment (SOFA) score (OR, 1.144; 95% CI, 1.086–1.206), trauma (OR, 0.172; 95% CI, 0.035–0.838), ΔP (OR, 1.077; 95% CI, 1.044–1.111), change in ΔP (OR, 1.087; 95% CI, 1.054–1.120), and change in MP (OR, 1.018; 95% CI, 1.006–1.029) were independently associated with 30-day mortality. Change in MP, change in ΔP, and SOFA scores were superior to ΔP in terms of the accuracy of predicting 30-day mortality. In conclusion, calculating change in ΔP is easy for respiratory therapists in clinical practice and may be used to predict mortality in patients with ARDS.

Background: Acute hypoxemic respiratory failure is common in intensive care units (ICUs). Lung biopsies may be required to make a definitive diagnosis in patients with unknown etiologies. The feasibility of transbronchial lung cryobiopsy is undetermined in patients with respiratory failure in the ICU. Methods: Patients who underwent bronchoscopy examinations with transbronchial lung cryobiopsy (TBLC) between July 2018 and December 2019 were retrospectively analyzed through medical chart review. The procedures were performed by well-experienced interventional pulmonologists. Results: Ten patients underwent bronchoscopy examinations with TBLC in the ICU at Chang Gung Memorial Hospital during the study period. In all patients, the diagnosis was made via pathological analysis. One patient developed pneumothorax and required chest tube placement after the procedure. None of the patients had bleeding requiring blood transfusion, and no deaths were directly related to the procedure. Conclusions: TBLC is a feasible technique to obtain lung pathology in patients with acute respiratory diseases of unknown etiologies. While the complication rate may be acceptable, the procedure should be performed by experienced interventional pulmonologists. However, airway blockers and fluoroscopy are highly recommended when used according to the current guideline. We do not encourage TBLC to be performed without having airway blockers available at the bedside.

Background: Disease severity may change in the first week after acute respiratory distress syndrome (ARDS) onset. The aim of this study was to evaluate whether the reclassification of disease severity after 48 h (i.e. day 3) of ARDS onset could help in predicting mortality and determine factors associated with ARDS persistence and mortality. Methods: We performed a secondary analysis of a 3-year prospective, observational cohort study of ARDS in a tertiary care referral center. Disease severity was reclassified after 48 h of enrollment, and cases that still fulfilled the Berlin criteria were regarded as nonresolving ARDS. Results: A total of 1034 ARDS patients were analyzed. Overall hospital mortality was 57.7% (56.7%, 57.5%, and 58.6% for patients with initial mild, moderate, and severe ARDS, respectively, p = 0.189). On day 3 reclassification, the hospital mortality rates were as follows: resolved (42.1%), mild (47.9%), moderate (62.4%), and severe ARDS (76.1%) ( p

Purpose. The aim of this study was to compare the metabolic load between adaptive support ventilation (ASV) and pressure support ventilation (PSV) modes in critically ill patients. Methods. Sequential 20 min ventilation by PSV followed by 20 min ASV in critically ill patients was assessed. ASV was set for full support, i.e., with the minute volume control set at the same level as the minute volume observed during PSV. The trial started from PSV 8 cmH2O and continued with high (PSV 12 cmH2O) to low (PSV 0) conditions or low to high conditions, in random order. The oxygen consumption (VO2), production of carbon dioxide (VCO2), and energy expenditure (EE) were measured by indirect calorimetry (IC). Results. Twenty-four patients with critical illness participated in the study. Comparing with the PSV mode, the EE in the ASV mode was lower in the level of PSV 0 cmH2O (1069 ± 73 vs. 1425 ± 76 kcal), PS 8 cmH2O (1116 ± 70 vs. 1284 ± 61 kcal), and PS 12 cmH2O (1017 ± 70 vs. 1169 ± 58 kcal) (p

Background and objectives: Patients with chronic obstructive pulmonary disease (COPD) suffer from impaired pulmonary function and dyspnea, which result in limited levels of physical activity, and impaired quality of life. Exercise and regular physical activity have been proven to break the vicious circle. The aim of this pilot study is to investigate the effects of a walking program on exercise capacity and quality of life in patients with COPD. Materials and Methods: Patients with COPD were randomly assigned to a pedometer group (PG) or control group (CON). Subjects in the PG walked target steps daily with a pedometer for six weeks. Before and after the program, the following measurements were performed: pulmonary function test (PFT), daily steps, Six-Minute Walk Test (6 MWT), COPD Assessment Test (CAT), and quality of life questionnaire (SF-12). Results: After this walking program, PG (n = 15) significantly improved their daily steps from 4768.4 ± 2643.3 steps to 7042.7 ± 4281.9 steps (p = 0.01). Forced vital capacity (FVC) increased from 2.5 ± 0.7 L to 2.8 ± 0.9 L (p = 0.02). CAT scores decreased from 14.9 ± 8.8 points to 11.5 ± 7.5 points (p = 0.03). In the control group (n = 11), there were no differences in any outcomes after this daily walking program. Conclusions: For patients with COPD, a daily walking program with a pedometer is beneficial in the improvement of pulmonary function, daily steps, and quality of life.

Critically ill patients, such as those in intensive care units (ICUs), can develop herpes simplex virus (HSV) pneumonitis. Given the high prevalence of acute respiratory distress syndrome (ARDS) and multiple pre-existing conditions among ICU patients with HSV pneumonitis, factors predicting mortality in this patient population require further investigation. In this retrospective study, the bronchoalveolar lavage or sputum samples of ICU patients were cultured or subjected to a polymerase chain reaction for HSV detection. Univariable and multivariable Cox regressions were conducted for mortality outcomes. The length of hospital stay was plotted against mortality on Kaplan–Meier curves. Among the 119 patients with HSV pneumonitis (age: 65.8 ± 14.9 years), the mortality rate was 61.34% (73 deaths). The mortality rate was significantly lower among patients with diabetes mellitus (odds ratio [OR] 0.12, 95% confidence interval [CI]: 0.02–0.49, p = 0.0009) and significantly higher among patients with ARDS (OR: 4.18, 95% CI: 1.05–17.97, p < 0.0001) or high (≥30) Acute Physiology and Chronic Health Evaluation II scores (OR: 1.08, 95% CI: 1.00–1.18, p = 0.02). Not having diabetes mellitus (DM), developing ARDS, and having a high Acute Physiology and Chronic Health Evaluation II (APACHE II) score were independent predictors of mortality among ICU patients with HSV pneumonitis.

Background: Obstetric patients comprise a limited portion of intensive care unit patients, but they often present with unfamiliar conditions and exhibit the potential for catastrophic deterioration. This study evaluated the maternal and neonatal outcomes of respiratory failure during pregnancy. Methods: Information on 71 patients at >25 weeks gestation in the ICU with respiratory failure was recorded between 2009 and 2013. The characteristics and outcomes of mothers and fetuses were determined through a retrospective chart review and evaluated using Student's t test, chi-square test, and Fisher's exact test. Results: The leading causes of respiratory failure were postpartum hemorrhage and severe preeclampsia in the obstetric causes group and pneumonia in the nonobstetric causes group during pregnancy and the peripartum period. The non-obstetric causes group exhibited a higher incidence of acute respiratory distress syndrome and renal replacement therapy as well as requiring more ventilator days. The patients in the obstetric causes group showed significant improvement after delivery in the partial pressure of arterial oxygen to the fraction of inspired oxygen and peak inspiratory pressure decrease. Both groups exhibited high incidences of neonatal respiratory distress syndrome. Neonatal complications resulting from meconium aspiration syndrome (MAS) and sepsis were more common in the non-obstetric causes group; however, neurological development impairment was more common in the obstetric causes group. Conclusion: Obstetric cause was associated with longer ventilator free days and fewer episodes of ARDS after delivery. Neonatal complications resulting from different etiologies of respiratory failure were found to differ. Keywords: Acute respiratory distress syndrome, Neonatal, Obstetric, Outcome, Respiratory failure

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome caused by direct (local damage to lung parenchyma) or indirect lung injury (insults from extrapulmonary sites with acute systemic inflammatory response), the clinical and biological complexity can have a profound effect on clinical outcomes. We performed a retrospective analysis of 152 severe ARDS patients receiving extracorporeal membrane oxygenation (ECMO). Our objective was to assess the differences in clinical characteristics and outcomes of direct and indirect ARDS patients receiving ECMO. Overall hospital mortality was 53.3%. A total of 118 patients were assigned to the direct ARDS group, and 34 patients were assigned to the indirect ARDS group. The 28-, 60-, and 90-day hospital mortality rates were significantly higher among indirect ARDS patients (all p < 0.05). Cox regression models demonstrated that among direct ARDS patients, diabetes mellitus, immunocompromised status, ARDS duration before ECMO, and SOFA score during the first 3 days of ECMO were independently associated with mortality. In indirect ARDS patients, SOFA score and dynamic compliance during the first 3 days of ECMO were independently associated with mortality. Our findings revealed that among patients receiving ECMO, direct and indirect subphenotypes of ARDS have distinct clinical outcomes and different predictors for mortality.

Extracorporeal membrane oxygenation (ECMO) is considered a salvage therapy in cases of severe acute respiratory distress syndrome (ARDS) with profound hypoxemia. However, the need for high-volume fluid resuscitation and blood transfusions after ECMO initiation introduces a risk of fluid overload. Positive fluid balance is associated with mortality in critically ill patients, and conservative fluid management for ARDS patients has been shown to shorten both the duration of mechanical ventilation and time spent in intensive care, albeit without a significant effect on survival. Nonetheless, few studies have addressed the influence of fluid balance on clinical outcomes in severe ARDS patients undergoing ECMO. In the current retrospective study, we examined the impact of cumulative fluid balance (CFB) on hospital mortality in 152 cases of severe ARDS treated using ECMO. Overall hospital mortality was 53.3%, and we observed a stepwise positive correlation between CFB and the risk of death. Cox regression models revealed that CFB during the first 3 days of ECMO was independently associated with higher hospital mortality (adjusted hazard ratio 1.110 [95% CI 1.027–1.201]; p = 0.009). Our findings indicate the benefits of a conservative treatment approach to avoid fluid overload during the early phase of ECMO when dealing with severe ARDS patients.

Abstract Background Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a valuable life support in acute respiratory distress syndrome (ARDS) in adult patients. However, the success of VV-ECMO is known to be influenced by the baseline settings of mechanical ventilation (MV) before its institution. This study was aimed at identifying the baseline ventilator parameters which were independently associated with hospital mortality in non-trauma patients receiving VV-ECMO for severe ARDS. Methods This retrospective study included 106 non-trauma patients (mean age: 53 years) who received VV-ECMO for ARDS in a single medical center from 2007 to 2016. The indication of VV-ECMO was severe hypoxemia (PaO2/ FiO2 ratio 35 cmH2O, positive end-expiratory pressure (PEEP) > 5 cmH2O, and FiO2 > 0.8. Important demographic and clinical data before and during VV-ECMO were collected for analysis of hospital mortality. Results The causes of ARDS were bacterial pneumonia (n = 41), viral pneumonia (n = 24), aspiration pneumonitis (n = 3), and others (n = 38). The median duration of MV before ECMO institution was 3 days and the overall hospital mortality was 53% (n = 56). The medians of PaO2/ FiO2 ratio, PIP, PEEP, and dynamic pulmonary compliance (PCdyn) at the beginning of MV were 84 mmHg, 32 cmH2O, 10 cmH2O, and 21 mL/cmH2O, respectively. However, before the beginning of VV-ECMO, the medians of PaO2/ FiO2 ratio, PIP, PEEP, and PCdyn became 69 mmHg, 36 cmH2O, 14 cmH2O, and 19 mL/cmH2O, respectively. The escalation of PIP and the declines in PaO2/ FiO2 ratio and PCdyn were significantly correlated with the duration of MV before ECMO institution. Finally, the duration of MV (OR: 1.184, 95% CI: 1.079–1.565, p

The high mortality rate of patients with severe acute respiratory distress syndrome (ARDS) warrants aggressive clinical intervention. Extracorporeal membrane oxygenation (ECMO) is a salvage therapy for life-threatening hypoxemia. Randomized controlled trials of ECMO for severe ARDS comprise a number of ethical and methodological issues. Therefore, indications and optimal timing for implementation of ECMO, and predictive risk factors for outcomes have not been adequately investigated. We performed propensity score matching to match ECMO-supported and non-ECMO-supported patients at 48 h after ARDS onset for comparisons based on clinical outcomes and hospital mortality. A total of 280 severe ARDS patients were included, and propensity score matching of 87 matched pairs revealed that the 90-d hospital mortality rate was 56.3% in the ECMO group and 74.7% in the non-ECMO group (p = 0.028). Subgroup analysis revealed that greater severity of ARDS, higher airway pressure, or a higher Sequential Organ Failure Assessment score tended to benefit from ECMO treatment in terms of survival. Multivariate logistic regression revealed that hospital mortality was significantly lower among patients who received ECMO than among those who did not. Our findings suggested that early initiation of ECMO (within 48 h) may increase the likelihood of survival for patients with severe ARDS.

Noninvasive positive pressure ventilation has been regarded as a strategy for improving exercise performance. Whether an increase in the ventilatory support level improves exercise performance in patients who have received invasive ventilation is unknown. The purpose of this study is to examine the effects of an additional level of pressure support (PS) ventilation on exercise tolerance in patients undergoing prolonged mechanical ventilation (PMV). Methods: This study examined 15 patients who were undergoing PMV. All patients performed an upper-arm exercise test at three PS levels: the baseline PS level (PS), a level 2 cmH2O higher than the baseline level (PS+2), and a level 4 cmH2O higher than the baseline level (PS+4). The physiological response, reasons for discontinuing the exercise test, and exercise duration were recorded and analyzed. Results: The tidal volume increased significantly from 271.7 ± 54.7 mL to 398.3 ± 88.7 mL at the PS+4 level (p = 0.01). Significant differences in exercise duration were observed at different PS levels. The exercise duration was significantly longer at the PS+4 level than at the PS and PS+2 levels (146.3 ± 139.9 seconds vs. 108.5 ± 85.9 seconds vs. 72.8 ± 43.9 seconds, p = 0.038) as their corresponding order. There were significant relationships between resting respiratory rate and exercise duration at the PS (r = −0.639, p = 0.034) and PS+2 levels (r = −0.668, p = 0.025). Conclusion: In patients undergoing PMV, an additional PS level of up to 4 cmH2O compared with the baseline setting may help to improve exercise tolerance by prolonging exercise duration.

In order to reduce the contamination in the ventilator, bacterial filters were placed on the expiratory limb of a ventilator circuit. Aerosolized mucolytic agents may increase the resistance of the ventilator. The goal of this study is to determine the impact of aerosolized mucolytic agents on the pressure change during mechanical ventilation. Methods: A lung model was investigated with mucolytic inhaled agents of 10% acetylcysteine and 2% hypertonic saline. The agents were administered using a jet nebulizer every 45 minutes for 15 minutes. The pressure drop was measured after nebulization. The end point was referred to the 45th dose or obstruction of the filter. Furthermore, the pressure drop after steam autoclaving was also measured. Results: The maximum pressure was significantly higher with 10% acetylcysteine than with 2% sodium chloride (39.32 ± 7.22 cmH2O vs. 3.53 ± 0.90 cmH2O, p

Diffuse alveolar damage (DAD) is a typical pathological finding of open lung biopsies in patients with acute respiratory distress syndrome (ARDS). Patients with ARDS and DAD have been reported to have a poorer prognosis than those without DAD. The aim of this study was to investigate the survival predictors in patients with ARDS and DAD.We retrospectively reviewed all ARDS patients who underwent an open lung biopsy which showed evidence of DAD from January 2006 to June 2015 at Chang Gung Memorial Hospital. Clinical data including baseline characteristics, medication, and survival outcomes were analyzed.A total of 64 ARDS patients with DAD were eligible for analysis and divided into known etiology (n = 17, 26.6%) and unknown etiology groups (n = 47, 73.4%). There was no significant difference in hospital mortality rate between the two groups (71.9% vs. 70.6%, p = 0.890). Univariate logistic regression analysis revealed that sequential organ failure assessment (SOFA) score at the time of a diagnosis of ARDS, and SOFA score, PaO2/FiO2 ratio, and positive end expiratory pressure level when the biopsy was performed were associated with hospital mortality. Multivariate analysis showed that the SOFA score on the day of the biopsy was an independent predictor of hospital mortality (odds ratio 1.413, 95% confidence interval 1.127-1.772; p = 0.03). There were no significant differences in the use, dose, duration and timing from ARDS to glucocorticoid therapy between the survivors and nonsurvivors.For selected ARDS patients who underwent an open lung biopsy with pathological DAD, SOFA score was an independent predictor of hospital mortality.

Objects: Invasive pulmonary mold infection usually has devastating outcomes. Timely differentiation between invasive pulmonary aspergillosis (IPA) from pulmonary mucormycosis (PM) is critical for treatment decision-making. However, information on IPA and PM differentiation is limited. Methods: We conducted a retrospective, multicenter, observational study, with proven and probable IPA and PM patients from January 2004 to December 2017. Demographics, clinical manifestations, image reports, histopathological findings, and outcomes were analyzed. Results: A total of 46 IPA (33 proven and 13 probable) and 19 PM (18 proven and one probable) cases were analyzed. The majority of tissues (81% in IPA and 61% in PM) were obtained using bronchoscopy. Prior influenza infection was a predisposing factor for IPA, and abscess formation in CT scan was associated with PM (p = 0.0491, p = 0.0454, respectively). The positive culture rate for PM was lower than that for IPA (37% vs. 67%, p = 0.0294). The galactomannan (GM) level from serum and bronchoalveolar lavage (BAL) fluid was significantly higher in IPA than in PM (3.3 ± 0.5 vs. 0.8 ± 0.6, p = 0.0361; 4.0 ± 0.6 vs. 0.59 ± 0.1, p = 0.0473, respectively). The overall mortality rate was 65%, which was similar among IPA and PM groups. Systemic steroid exposure and high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores on admission were independently correlated to mortality in IPA (p = 0.027, p = 0.026, respectively). However, there was no predictor for mortality found in PM patients. Conclusions: Influenza infection, abscess formation in CT scan, and GM level may help physicians to differentiate IPA and PM. Bronchoscopy-guided biopsy and lavage specimen provide timely and definite diagnosis. The prognosis of IPA is associated with systemic steroid exposure and higher APACHE II scores on admission.

Although aerosol delivery through mechanical ventilators has been used to administer various medications, little is known of administration with colistin. This in vitro evaluation aimed to evaluate size distribution of colistin delivery by different types of nebulizers and concentrations during mechanical ventilation. Colistin methanesulfonate (colistin) for injection was dissolved in 6 mL of distilled water to produce a low concentration (L; 156 mg) and a high concentration (H; 312 mg). A dose volume of 6 mL was placed in a vibrating mesh nebulizer (VMN) and a jet nebulizer (JN). The inhaled mass (mean ± SD) of the VMN-L (53.80 ± 14.79 mg) was greater than both the JN-L (19.82 ± 3.34 mg, P = 0.001) and JN-H (31.72 ± 4.48 mg, P = 0.017). The nebulization time of the VMN-L (42.35 ± 2.30 min) was two times longer than the JN-L (21.12 ± 0.8 min) or JN-H (21.65 ± 0.42 min; P < 0.001). The mass median aerodynamic distal to the endotracheal tube was within a similar range at 2.03 to 2.26 μm (P = 0.434), independent of neb or formulation concentration. In conclusion, the VMN-L yields greater inhaled mass than the JN with either concentration. Therefore, a standard nominal dose of colistin results in a higher delivered dose during mechanical ventilation with a VMN compared with a JN and may be considered the preferred device. If JN must be used, multiple doses of low concentration colistin may compensate for poor delivery performance.

Common complications in PMV include changes in the airway clearance mechanism, pulmonary function, and respiratory muscle strength, as well as chest radiological changes such as atelectasis. Lung expansion therapy which includes IPPB and PEEP prevents and treats pulmonary atelectasis and improves lung compliance. Our study presented that patients with PMV have improvements in lung volume and oxygenation after receiving IPPB therapy. The combination of IPPB and PEEP therapy also results in increase in respiratory muscle strength. The application of IPPB facilitates the homogeneous gas distribution in the lung and results in recruitment of collapsed alveoli. PEEP therapy may reduce risk of respiratory muscle fatigue by preventing premature airway collapse during expiration. The physiologic effects of IPPB and PEEP may result in enhancement of pulmonary function and thus increase the possibility of successful weaning from mechanical ventilator during weaning process. For patients with PMV who were under the risk of atelectasis, the application of IPPB may be considered as a supplement therapy for the enhancement of weaning outcome during their stay in the hospital.

Delayed diagnosis and isolation increases the risk of nosocomial transmission of tuberculosis (TB). To assess the risk of delayed management of TB, we analyzed the risk factors of prolonged delay in isolation of smear-positive TB patients in pulmonology/infectious diseases and other wards in a tertiary teaching hospital. Methods: We enrolled smear-positive TB patients aged > 16 years with delayed respiratory isolation following hospitalization. Medical records were reviewed retrospectively. Time intervals between admission, order of sputum acid-fast staining, initiation of anti-tuberculous treatment and isolation were compared between pulmonology/infectious diseases wards (PIWs) and other wards. Risk factors were analyzed in patients with prolonged isolation delay of > 7 days in individual groups. Results: Isolation was delayed in 191 (73.7%) of 259 hospitalized smear-positive TB patients. Median suspicion, treatment and isolation delays were 0, 3 and 4 days in PIWs and 1, 5 and 7 days in other wards. For patients admitted to non-PIWs, atypical chest radiographs, symptoms without dyspnea or not being admitted from the emergency department (ED) were risk factors for prolonged isolation delay exceeding 7 days. The only risk factor for delayed isolation in patients admitted to PIWs was age ≥ 70 years. Conclusion: Delays in suspicion, treatment and isolation of TB patients were longer in non-PIWs. Clinicians should be alert to those admitted to non-PIWs with atypical chest radiographs, atypical symptoms, or not admitted from the ED.

Respiratory distress syndrome resulting from leukemic pulmonary infiltrates is seldom diagnosed antemortem. Two 60- and 80-year-old women presented with general malaise, progressive shortness of breath, and hyperleukocytosis, which progressed to acute respiratory distress syndrome (ARDS) after admission. Acute leukemia with pulmonary infection was initially diagnosed, but subsequent examinations including open lung biopsy revealed leukemic pulmonary infiltrates without infection. In one case, the clinical condition and chest radiography improved initially after combination therapy with chemotherapy for leukemia and aggressive pulmonary support. However, new pulmonary infiltration on chest radiography and hypoxemia recurred, which was consistent with acute lysis pneumopathy. Despite aggressive treatment, both patients died due to rapidly deteriorating condition. Leukemic pulmonary involvement should be considered in acute leukemia patients with non-infectious diffusive lung infiltration, especially in acute leukemia with a high blast count.

To evaluate the ICU mortality rate of mechanically ventilated hematopoietic stem cell transplantation (HSCT) recipients and to identify the factors that were associated with ICU mortality. The impact of surgical lung biopsy (SLB) in patients with unexplained pulmonary infiltrates was also evaluated. Methods: Forty-one mechanically ventilated HSCT recipients admitted to the ICU during the study period were enrolled. The medical records were reviewed and data at ICU admission were analyzed. Data were compared between ICU survivors and nonsurvivors. The pathologic findings of SLB and the resulting impact on treatment were analyzed. Results: Eight patients (19.5%) survived the ICU stay, and seven (17%) lived to hospital discharge. The most common etiologies of ICU mortality included bacterial pneumonia, cytomegalovirus pneumonia, diffuse alveolar hemorrhage, sepsis, and aspergillosis. The factors associated with higher mortality were older age when performing HSCT, older age at ICU admission, higher acute physiology and chronic health evaluation (APACHE) II score, shock, higher respiratory rate, and higher heart rate at the time of ICU admission. Ten patients underwent SLB which resulted in treatment changes in five of them. Three patients had complications of SLB and one patient died of complications. Conclusion: The ICU mortality rate of mechanically ventilated HSCT recipients was high. Factors associated with ICU mortality were older age, high APACHE II score, presence of shock, and higher respiratory or heart rate at the time of ICU admission. SLB might provide specific diagnosis in HSCT recipients with unexplained pulmonary infiltrates and aid modification of treatment. [J Formos Med Assoc 2007;106(4):295-301]

Gamma-secretase-mediated Notch3 signaling is involved in smooth muscle cell (SMC) hyper-activity and proliferation leading to pulmonary arterial hypertension (PAH). In addition, Propylthiouracil (PTU), beyond its anti-thyroid action, has suppressive effects on atherosclerosis and PAH. Here, we investigated the possible involvement of gamma-secretase-mediated Notch3 signaling in PTU-inhibited PAH. In rats with monocrotaline-induced PAH, PTU therapy improved pulmonary arterial hypertrophy and hemodynamics. In vitro, treatment of PASMCs from monocrotaline-treated rats with PTU inhibited their proliferation and migration. Immunocyto, histochemistry, and western blot showed that PTU treatment attenuated the activation of Notch3 signaling in PASMCs from monocrotaline-treated rats, which was mediated via inhibition of gamma-secretase expression especially its presenilin enhancer 2 (Pen-2) subunit. Furthermore, over-expression of Pen-2 in PASMCs from control rats increased the capacity of migration, whereas knockdown of Pen-2 with its respective siRNA in PASMCs from monocrotaline-treated rats had an opposite effect. Transfection of PASMCs from monocrotaline-treated rats with Pen-2 siRNA blocked the inhibitory effect of PTU on PASMC proliferation and migration, reflecting the crucial role of Pen-2 in PTU effect. We present a novel cell-signaling paradigm in which overexpression of Pen-2 is essential for experimental pulmonary arterial hypertension to promote motility and growth of smooth muscle cells. Propylthiouracil attenuates experimental PAH via suppression of the gamma-secretase-mediated Notch3 signaling especially its presenilin enhancer 2 (Pen-2) subunit. These findings provide a deep insight into the pathogenesis of PAH and a novel therapeutic strategy.

BACKGROUND: High tidal volume (VT) mechanical ventilation (MV) can induce the recruitment of neutrophils, release of inflammatory cytokines and free radicals, and disruption of alveolar epithelial and endothelial barriers. It is proposed to be the triggering factor that initiates ventilator-induced lung injury (VILI) and concomitant hyperoxia further aggravates the progression of VILI. The Src protein tyrosine kinase (PTK) family is one of the most critical families to intracellular signal transduction related to acute inflammatory responses. The anti-inflammatory abilities of induced pluripotent stem cells (iPSCs) have been shown to improve acute lung injuries (ALIs); however, the mechanisms regulating the interactions between MV, hyperoxia, and iPSCs have not been fully elucidated. In this study, we hypothesize that Src PTK plays a critical role in the regulation of oxidants and inflammation-induced VILI during hyperoxia. iPSC therapy can ameliorate acute hyperoxic VILI by suppressing the Src pathway. METHODS: Male C57BL/6 mice, either wild-type or Src-deficient, aged between 2 and 3 months were exposed to high VT (30 mL/kg) ventilation with or without hyperoxia for 1 to 4 h after the administration of Oct4/Sox2/Parp1 iPSCs at a dose of 5×10(7) cells/kg of mouse. Nonventilated mice were used for the control groups. RESULTS: High VT ventilation during hyperoxia further aggravated VILI, as demonstrated by the increases in microvascular permeability, neutrophil infiltration, macrophage inflammatory protein-2 (MIP-2) and plasminogen activator inhibitor-1 (PAI-1) production, Src activation, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and malaldehyde (MDA) level. Administering iPSCs attenuated ALI induced by MV during hyperoxia, which benefited from the suppression of Src activation, oxidative stress, acute inflammation, and apoptosis, as indicated by the Src-deficient mice. CONCLUSION: The data suggest that iPSC-based therapy is capable of partially suppressing acute inflammatory and oxidant responses that occur during hyperoxia-augmented VILI through the inhibition of Src-dependent signaling pathway.

BACKGROUNDHigh-tidal-volume mechanical ventilation used in patients with acute lung injury (ALI) can induce the release of inflammatory cytokines, as macrophage inflammatory protein-2 (MIP-2), recruitment of neutrophils, and disruption of alveolar epithelial and endothelial barriers. Induced pluripotent stem cells (iPSCs) have been shown to improve ALI in mice, but the mechanisms regulating the interactions between mechanical ventilation and iPSCs are not fully elucidated. Nuclear factor kappa B (NF-κB) and NF-κB repressing factor (NKRF) have been proposed to modulate the neutrophil activation involved in ALI. Thus, we hypothesized intravenous injection of iPSCs or iPSC-derived conditioned medium (iPSC-CM) would decrease high-tidal-volume ventilation-induced neutrophil infiltration, oxidative stress, and MIP-2 production through NF-κB/NKRF pathways.METHODSMale C57BL/6 mice, aged between 6 and 8 weeks, weighing between 20 and 25 g, were exposed to high-tidal-volume (30 ml/kg) mechanical ventilation with room air for 1 to 4 h after 5×10(7) cells/kg mouse iPSCs or iPSC-CM administration. Nonventilated mice were used as control groups.RESULTSHigh-tidal-volume mechanical ventilation induced the increases of integration of iPSCs into the injured lungs of mice, microvascular permeability, neutrophil infiltration, malondialdehyde, MIP-2 production, and NF-κB and NKRF activation. Lung injury indices including inflammation, lung edema, ultrastructure pathologic changes and functional gas exchange impairment induced by mechanical ventilation were attenuated with administration of iPSCs or iPSC-CM, which was mimicked by pharmacological inhibition of NF-κB activity with SN50 or NKRF expression with NKRF short interfering RNA.CONCLUSIONSOur data suggest that iPSC-based therapy attenuates high-tidal-volume mechanical ventilation-induced lung injury, at least partly, through inhibition of NF-κB/NKRF pathways. Notably, the conditioned medium of iPSCs revealed beneficial effects equal to those of iPSCs.