Animals ; Aquaporins/metabolism* ; Disease Models, Animal ; Glycoproteins/pharmacology* ; Humans ; Lung/metabolism* ; Protective Agents/pharmacology* ; Respiratory Distress Syndrome/physiopathology* ; Sus scrofa ; Trypsin Inhibitors/pharmacology* ; Up-Regulation

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.
Adoptive Transfer ; Alveolar Epithelial Cells ; pathology ; Animals ; Apoptosis ; Betacoronavirus ; Body Fluids ; metabolism ; CD4-Positive T-Lymphocytes ; immunology ; Clinical Trials as Topic ; Coinfection ; prevention & control ; therapy ; Coronavirus Infections ; complications ; immunology ; Disease Models, Animal ; Endothelial Cells ; pathology ; Extracorporeal Membrane Oxygenation ; Genetic Therapy ; methods ; Genetic Vectors ; administration & dosage ; therapeutic use ; Humans ; Immunity, Innate ; Inflammation Mediators ; metabolism ; Lung ; pathology ; physiopathology ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stem Cells ; physiology ; Multiple Organ Failure ; etiology ; prevention & control ; Pandemics ; Pneumonia, Viral ; complications ; immunology ; Respiratory Distress Syndrome, Adult ; immunology ; pathology ; therapy ; Translational Medical Research

OBJECTIVETo compare the therapeutic effects of high-frequency oscillatory ventilation+pulmonary surfactant (HFOV+PS), conventional mechanical ventilation+pulmonary surfactant (CMV+PS), and conventional mechanical ventilation (CMV) alone for acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in neonates.

METHODSA total of 136 neonates with ALI/ARDS were enrolled, among whom 73 had ALI and 63 had ARDS. They were divided into HFOV+PS group (n=45), CMV+PS group (n=53), and CMV group (n=38). The neonates in the first two groups were given PS at a dose of 70-100 mg/kg. The partial pressure of oxygen (PaO), partial pressure of carbon dioxide (PaCO), PaO/fraction of inspired oxygen (FiO), oxygenation index (OI), and respiratory index (RI) were measured at 0, 12, 24, 48, and 72 hours of mechanical ventilation.

RESULTSAt 12, 24, and 48 hours of mechanical ventilation, the HFOV+PS group had higher PaOand lower PaCOthan the CMV+PS and CMV groups (P<0.05). At 12, 24, 48, and 72 hours of mechanical ventilation, the HFOV+PS group had higher PaO/FiOand lower OI and RI than the CMV+PS and CMV groups (P<0.05). The HFOV+PS group had shorter durations of mechanical ventilation and oxygen use than the CMV+PS and CMV groups (P<0.05). There were no significant differences in the incidence rates of air leakage and intracranial hemorrhage and cure rate between the three groups.

CONCLUSIONSIn neonates with ALI/ARDS, HFOV combined with PS can improve pulmonary function more effectively and shorten the durations of mechanical ventilation and oxygen use compared with CMV+PS and CMV alone. It does not increase the incidence of complications.

Acute Lung Injury ; physiopathology ; therapy ; Combined Modality Therapy ; Female ; High-Frequency Ventilation ; Humans ; Infant, Newborn ; Male ; Pulmonary Surfactants ; therapeutic use ; Respiratory Distress Syndrome, Newborn ; physiopathology ; therapy ; Respiratory Mechanics

PURPOSEThis prospective observational study aims to evaluate the accuracy of dead-space fraction derived from the ventilator volumetric capnography (volumetric CO₂) or a prediction equation to predict the survival of mechanically ventilated patients with acute respiratory distress syndrome (ARDS).

METHODSConsecutive VD/VT measurements were obtained based upon a prediction equation validated by Frankenfield et al for dead-space ventilation fraction: VD/VT = 0.320 + 0.0106 (PaCO₂-ETCO₂)⁺ 0.003 (RR)⁺0.0015 (age) in adult patients who had infection-related severe pneumonia and were confirmed as having ARDS. Here PaCO₂ is the arterial partial pressure of carbon dioxide in mmHg; ETCO₂, the end- tidal carbon dioxide measurement in mmHg; RR, respiratory rate per minute; and age in years. Once the patient had intubation, positive end expiratory pressure was adjusted and after Phigh reached a steady state, VD/VT was measured and recorded as the data for the first day. VD/VT measurement was repeated on days 2, 3, 4, 5 and 6. Meanwhile we collected dead-space fraction directly from the ventilator volu- metric CO₂ and recorded it as Vd/Vt. We analyzed the changes in VD/VT and Vd/Vt over the 6-day period to determine their accuracy in predicting the survival of ARDS patients.

RESULTSOverall, 46 patients with ARDS met the inclusion criteria and 24 of them died. During the first 6 days of intubation, VD/VT was significantly higher in nonsurvivors on day 4 (0.70 ± 0.01 vs 0.57 ± 0.01), day 5 (0.73 ± 0.01 vs. 0.54 ± 0.01), and day 6 (0.73 ± 0.02 vs. 0.54 ± 0.01) (all p =0.000). Vd/Vt showed no significant difference on days 1e4 but it was much higher in nonsurvivors on day 5 (0.45 ± 0.04 vs. 0.41 ± 0.06) and day 6 (0.47 ± 0.05 vs. 0.40 ± 0.03) (both p=0.008). VD/VT on the fourth day was more accurate to predict survival than Vd/Vt. The area under the receiver-operating characteristic curve for VD/VT and Vd/Vt in evaluating ARDS patients survival was day 4 (0.974 ± 0.093 vs. 0.701 ± 0.023, p = 0.0024) with the 95% confidence interval being 0.857-0.999 vs. 0.525-0.841.

CONCLUSIONCompared with Vd/Vt derived from ventilator volumetric CO₂, VD/VT on day 4 calculated by Frankenfield et al's equation can more accurately predict the survival of ARDS patients.

Adult ; Capnography ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; ROC Curve ; Respiration, Artificial ; Respiratory Dead Space ; physiology ; Respiratory Distress Syndrome, Adult ; mortality ; physiopathology

OBJECTIVETo investigate the pulmonary function after treatment in neonates with respiratory distress syndrome (RDS) at varying disease severity levels and different gestational ages.

METHODSA total of 107 neonates with RDS were divided into <34 weeks group (65 neonates), late preterm group (21 neonates), full-term group (21 neonates). Another 121 non-RDS children were enrolled as the control group. According to the severity of RDS, the RDS neonates were divided into mild RDS group (grades 1 and 2; 76 neonates), and severe RDS (grades 3 and 4; 21 neonates). The tidal breathing pulmonary function was measured at a corrected gestational age of 44weeks.

RESULTSThe pulmonary function parameters showed no significant differences across the groups of RDS neonates of different gestational ages; the tidal volume per kilogram of body weight (VT/kg) showed no significant difference between the RDS and non-RDS groups, while the RDS group had significantly higher ratio of time to peak tidal expiratory flow to total expiratory time (tPTEF/tE) and ratio of volume to peak tidal expiratory flow to total expiratory volume (vPTEF/vE) than the non-RDS group of the same gestational age (P<0.05). At a corrected gestational age of 44 weeks, the two groups of neonates with varying severity levels of RDS had significantly lower tPTEF/tE and vPTEF/vE than the control group (P<0.05), and tPTEF/tE and vPTEF/vE tended to decrease with the increasing severity level of RDS.

CONCLUSIONSNeonates with RDS have significantly decreased pulmonary function than those without RDS. At a corrected gestational age of 44 weeks, the tidal breathing pulmonary function in neonates with RDS is not associated with gestational age, but is associated with the severity of RDS.

Female ; Gestational Age ; Humans ; Infant, Newborn ; Lung ; physiopathology ; Male ; Respiratory Distress Syndrome, Newborn ; physiopathology

Among the fire victims, respiratory tract injury resulted from smoke inhalation is the major cause of death. Particulate substances in smoke, toxic and harmful gas, and chemical substances act together would rapidly induce the occurrence of dramatic pathophysiologic reaction in the respiratory tract, resulting in acute injury to the respiratory tract, thus inducing serious injury to it and acute respiratory distress syndrome, leading to death of the victims. In recent years, the pathophysiologic mechanism of severe smoke inhalation injury has been gradually clarified, thus appreciable advances in its treatment have been achieved. This paper is a brief review of above-mentioned aspects.
Burns, Inhalation ; pathology ; physiopathology ; Fires ; Humans ; Respiratory Distress Syndrome, Adult ; physiopathology ; Smoke ; adverse effects ; Smoke Inhalation Injury ; pathology ; physiopathology

OBJECTIVETo study clinical characteristics and evaluate cardiac hemodynamic changes in premature infants with patent ductus ateriosus (PDA).

METHODOne hundred and five infants born at ≤ 34 weeks' gestational age (GA) and ≤2 000 g birth weight (BW) were prospectively enrolled, including 63 males and 42 females, and the mean GA was (31. 1 ± 1.9) weeks and BW (1 401 ± 314) g. Echocardiography was done to detect hemodynamically significant PDA (hsPDA) and to evaluate left ventricular function at 2, 3, 5 and 7 d respectively after birth. On the basis of clinical symptoms and echocardiographic outcome, all the cases were divided into 3 groups: hsPDA group (n = 34), non-hsPDA (nhsPDA) group (n = 44) and non-PDA (nPDA) group (n = 27) to survey and compare general conditions, DA diameter, shunt direction, left ventricular function and complications.

RESULTThe hsPDA group had smaller GA ((30. 5 ± 2. 1) vs. (31. 6 ± 1. 6) weeks, P = 0. 01) and greater proportion of pulmonary surfactant use and mechanical ventilation (2, 3, 5 d of birth) than the nhsPDA and the nPDA group (χ2 = 11. 62, 14. 95, 12. 73, 1:1. 59, P = 0. 00; 0. 00, 0. 01, 0. 01). Univariate and multivariate Logistic regression analysis indicated that the average length of stay (ALOS) was correlated with hsPDA (F =3. 52 and P =0. 03, OR 1. 03 and P =0. 02). The ALOS was longer in the hsPDA group than in the nhsPDA and the nPDA group ((39 ±23)vs. (30 ± 16)and(29 ±13) d, P =0.02, 0.03). There was no significant.difference in rates of mortality/giving-up of treatment among the three groups (5. 9% (2/34)vs. 0 (0/44) and 3. 7% (1/27), χ2 = 5. 26, P = 0. 06). Diastolic blood pressure and mean blood pressure were significantly lower in the hsPDA group than in the other two groups (P all <0. 05) at 2, 3 and 5 days after birth and the pulse pressure was found significantly higher in the hsPDA group than in the nPDA group at 2 d after birth. Univariate and multivariate Logistic regression analysis demonstrated that hsPDA was correlated significantly with neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD) (χ2 =7. 34 and 7. 39, P = 0. 02 and 0. 02; OR = 3. 46 and 4. 01, P = 0. 04 and 0. 02). Premature infants with hsPDA had normal left ventricular fractional shortening (FS) and left ventricular ejection fraction (LVEF), although the cardiac output (CO) of left ventricle increased significantly(F = 6. 93, P <0. 01) within seven days of birth. There was no significant difference in cardiac hemodynamic parameters among closed group of hsPDA group, nhsPDA group and nPDA group simutaneously reexamined at 7th day after birth. The CO was extremely significantly different among premature infants who had different GAs and BWs. The lower the GAs and the BWs, the lower the value of CO(F =5. 16 and 14. 87, P all <0. 01). The DA diameter was reduced much more dramatically after ibuprofen treatment than before in hsPDA group(t = 5. 58, P <0. 01).

CONCLUSIONThe GA, PS use and mechanical ventilation were probably associated with hsPDA. The mean blood pressure and diastolic blood pressure were decreased and pulse pressure was increased in preterm infants with hsPDA that correlated significantly with ALOS, NRDS and BPD. In addition, increased CO values were found in hsPDA group. Oral ibuprofen administered to preterm infants for hsPDA at > 24 h of life promoted ductal closure.

Birth Weight ; Bronchopulmonary Dysplasia ; Cardiac Output ; Cyclooxygenase Inhibitors ; therapeutic use ; Ductus Arteriosus, Patent ; physiopathology ; Echocardiography ; Female ; Gestational Age ; Hemodynamics ; Humans ; Ibuprofen ; therapeutic use ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; Male ; Pulmonary Surfactants ; Respiration, Artificial ; Respiratory Distress Syndrome, Newborn ; Ventricular Function, Left

The effect of high frequency oscillatory ventilation (HFOV) at early stage on hemodynamic parameters, extravascular lung water (EVLW), lung capillary permeability, CC16 and sICAM-1 in piglets with pulmonary or extrapulmonary acute respiratory distress syndrome (ARDS) was explored. Central vein pressure (CVP) and pulse indicator continuous cardiac output (PiCCO) were monitored in 12 anesthetized and intubated healthy piglets. Pulmonary ARDS (ARDSp) and extrapulmonary ARDS (ARDSexp) models were respectively established by lung lavage of saline solution and intravenous injection of oleic acid. Then the piglets received HFOV for 4 h. EVLW index (EVLWI), EVLW/intratroracic blood volume (ITBV) and pulmonary vascular permeability index (PVPI) were measured before and after modeling (T0 and T1), and T2 (1 h), T3 (2 h), T4 (3 h) and T5 (4 h) after HFOV. CC16 and sICAM-1 were also detected at T1 and T5. Results showed at T1, T3, T4 and T5, EVLWI was increased more significantly in ARDSp group than in ARDSexp group (P<0.05). The EVLWI in ARDSp group was increased at T1 (P=0.008), and sustained continuously within 2 h (P=0.679, P=0.216), but decreased at T4 (P=0.007) and T5 (P=0.037). The EVLWI in ARDSexp group was also increased at T1 (P=0.003), but significantly decreased at T3 (P=0.002) and T4 (P=0.019). PVPI was increased after modeling in both two groups (P=0.004, P=0.012), but there was no significant change within 4 h (T5) under HFOV in ARDSp group, while PVPI showed the increasing trends at first, then decreased in ARDSexp group after HFOV. The changes of EVLW/ITBV were similar to those of PVPI. No significant differences were found in ΔEVLWI (P=0.13), ΔPVPI (P=0.28) and ΔEVLW/ITBV between the two groups (P=0.63). The significant decreases in both CC16 and sICAM-1 were found in both two groups 4 h after HFOV, but there was no significant difference between the two groups. It was concluded that EVLWI and lung capillary permeability were markedly increased in ARDSp and ARDSexp groups. EVLW could be decreased 4 h after the HFOV treatment. HFOV, EVLW/ITBV and PVPI were increased slightly at first, and then decreased in ARDSexp group, while in ARDSp group no significant difference was found after modeling. No significant differences were found in the decreases in EVLW and lung capillary permeability 4 h after HFOV.
Animals ; Capillaries ; physiopathology ; High-Frequency Ventilation ; Lung ; blood supply ; Respiratory Distress Syndrome, Adult ; physiopathology ; Swine

OBJECTIVETo understand the effect of lung recruitment maneuver (LRM) with positive end-expiratory pressure (PEEP) on oxygenation and outcomes in preterm infants with respiratory distress syndrome (RDS) ventilated by proportional assist ventilation (PAV).

METHODFrom January 2012 to June 2013, thirty neonates with a diagnosis of RDS who required mechanical ventilation were divided randomly into LRM group (n=15, received an LRM and surport by PAV) and control group (n=15, only surport by PAV). There were no statistically significant differences in female (7 vs. 6); gestational age [(29.3±1.2) vs. (29.5±1.1) weeks]; body weight[(1,319±97) vs. (1,295±85) g]; Silverman Anderson(SA) score for babies at start of ventilation (7.3±1.2 vs. 6.9±1.4); initial FiO2 (0.54±0.12 vs. 0.50±0.10) between the two groups (all P>0.05). LRM entailed increments of 0.2 cmH2O (1 cmH2O=0.098 kPa) PEEP every 5 minutes, until fraction of inspired oxygen (FiO2)=0.25. Then PEEP was reduced and the lung volume was set on the deflation limb of the pressure/volume curve.When saturation of peripheral oxygen fell and FiO2 rose, we reincremented PEEP until SpO2 became stable. The related clinical indicators of the two group were observed.

RESULTThe doses of surfactant administered (1.1±0.3 vs. 1.5±0.5, P=0.027), Lowest FiO2 (0.29±0.05 vs. 0.39±0.06, P=0.000), time to lowest FiO2[ (103±18) vs. (368±138) min, P=0.000] and O2 dependency [(7.6±1.0) vs.( 8.8±1.3) days, P=0.021] in LRM group were lower than that in control group (all P<0.05). The maximum PEEP during the first 12 hours of life [(8.4±0.8) vs. (6.8±0.8) cmH2O, P=0.000] in LRM group were higher than that in control group (P<0.05). FiO2 levels progressively decreased (F=35.681, P=0.000) and a/AO2 Gradually increased (F=37.654, P=0.000). No adverse events and no significant differences in the outcomes were observed.

CONCLUSIONLRM can reduce the doses of pulmonary surfactant administered, time of the respiratory support and the oxygen therapy in preterm children with RDS.

Female ; Humans ; Infant, Newborn ; Infant, Premature ; Interactive Ventilatory Support ; methods ; Lung ; physiopathology ; Male ; Oxygen ; administration & dosage ; Oxygen Inhalation Therapy ; Positive-Pressure Respiration ; methods ; Pulmonary Surfactants ; administration & dosage ; Respiration ; Respiration, Artificial ; Respiratory Distress Syndrome, Newborn ; physiopathology ; therapy ; Tidal Volume ; Treatment Outcome

OBJECTIVETo evaluate the clinical value of the pulse indicator continuous cardiac output (PiCCO) system in patients with severe acute pancreatitis (SAP) complicated with acute respiratory distress syndrome (ARDS).

METHODTwo cases of SAP with ARDS were monitored using PiCCO during comprehensive management in the Pediatric Intensive Care Unit (PICU) of Shengjing Hospital, China Medical University. To guide fluid management, the cardiac index (CI) was measured to assess cardiac function, the global end-diastolic volume index (GEDVI) was used to evaluate cardiac preload, and the extravascular lung water index (EVLWI) was used to evaluate the pulmonary edema.

RESULTCase 1 was diagnosed with type L2 acute lymphoblastic leukemia (intermediate risk) and received the sixth maintenance phases of chemotherapy this time. After a 1-week dosage of chemotherapeutic drugs (pegaspargase and mitoxantrone), he suffered SAP combined with ARDS. Except comprehensive treatment (life supporting, antibiotic, etc.) and applying continuous veno-venous hemodiafiltration (CVVHDF) to remove inflammatory mediators. PiCCO monitor was utilized to guide fluid management. During the early stage of PiCCO monitoring, the patient showed no significant manifestations of pulmonary edema in the bedside chest X-ray (bedside ultrasound showed left pleural effusion), and had an oxygenation index 223 mmHg (1 mmHg = 0.133 kPa), GEDVI 450 ml/m², and ELVWI 7 ml/kg. We increased cardiac output to increase tissue perfusion and dehydration speed of CVVHDF was set at 70 ml/h. Two hours later, GEDVI significantly increased to 600 ml/m² and ELVWI significantly increased to 10 ml/kg, the oxygenation index declined to 155 mmHg, the bedside chest X-ray showed a significant decrease of permeability (right lung) and PEEP was adjusted to 5 cmH₂O (1 cmH₂O = 0.098 kPa), indicating circulating overload. ARDS subsequently occurred, upon which the fluid infusion was halted, the dehydration rate of CVVHDF raised (adjusted to 100-200 ml/h). On day 3 in the PICU, EVLWI dropped to 6 ml/kg, GEDVI dropped to 370 ml/m², and the oxygenation index increased to 180 mmHg. On day 8, the patient was successfully weaned from the ventilator. However, on day 9, the patient reverted to mechanical ventilation due to secondary infection. On day 30, the patient was discharged for voluntarily giving up treatment. Late follow-up results showed that the patient was dead one day after giving up treatment. Case 2 was admitted due to SAP induced by overeating one day before admission. On day 2, the patient showed dyspnea and oxygen saturation decreased to 80%. We applied mechanical ventilation, CVVHDF to remove inflammatory mediators and PiCCO to guide fluid management. According to the initial data of PiCCO, EVLWI was 9 ml/kg, GEDVI was 519 ml/m², the oxygenation index was 298 mmHg, the bedside chest X-ray showed decreased permeability and PEEP was adjusted to 5 cmH₂O, suggesting the existence of ARDS. During treatment, the dehydration speed of CVVHDF was set at 50 ml/h to maintain the balance of fluid input and output. Two hours after PiCCO monitoring, the oxygenation index decreased to 140 mmHg, GEDVI 481 ml/m², EVLWI 9 ml/kg, thus the dehydration speed of CVVHDF was increased (up to 100 ml/h). On day 4 in the PICU, EVLWI was 9 ml/kg, GEDVI was 430 ml/m², oxygenation index was 394 mmHg, and the bedside chest X-ray showed that permeability was higher. On day 5, the patient was transferred from PiCCO. On day 30, the patient recovered and was discharged.

CONCLUSIONPiCCO monitoring can provide real-time surveillance of cardiac function, cardiac preload and afterload, and extravascular lung water in pediatric patients with SAP combined with ARDS. These results are clinically significant for the rescue of critically ill patients with ARDS or shock.

Acute Disease ; Cardiac Output ; physiology ; Child ; China ; Critical Illness ; Extravascular Lung Water ; Fluid Therapy ; Heart ; physiology ; Heart Rate ; Humans ; Lung ; physiology ; Monitoring, Physiologic ; methods ; Pancreatitis ; complications ; physiopathology ; therapy ; Pulmonary Edema ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult ; complications ; physiopathology ; Severity of Illness Index ; Treatment Outcome