ObjectiveTo assesse the association of an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) with the risk and the mortality of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS).
MethodsWe searched electronic databases through April 2014 for the terms "angiotensin-converting enzyme gene", "acute lung injury" and "acute respiratory distress syndrome", and reviewed all studies that reported the relationship of the I/D polymorphism in ACE with ALI/ARDS in adults. Eight studies met the inclusion criteria, comprising 498 ALI/ARDS patients, 3220 healthy controls and 1137 patients without ALI/ARDS. Three genetic models were used: the allele, dominant and recessive models. The meta-analysis was performed with RevMan 5.2 software.
ResultsThe ACE I/D polymorphism was not associated with susceptibility to ALI/ARDS compared with the healthy controls and the patient controls for any genetic model. The ACE I/D polymorphism was associated with the mortality risk of ALI/ARDS in Asian subjects, and OR was 2.99 (95% CI 1.87-4.76, P < 0.05), 0.36 (95% CI 0.20-0.67, P < 0.05), 4.62 (95% CI 1.71-12.45, P < 0.05) for allele I/D, genotype II/II+ID and genotype DD/II+ID, respectively.
ConclusionThere is a possible association between the ACE I/D polymorphism genotype and the mortality risk of ALI/ARDS in Asians.
Objective To investigate the serumlevel of endothelin-1 ( ET-1) in patients with acute lung injury/acute respiratory distress syndrome ( ALI/ARDS) and its clinical significance. Methods Thirty-one ALI/ARDS patients received mechanical ventilation in ICUand 25 normal subjects were recruited in the study. The patients who died in two weeks fell in death group, and the patients who did not died in two weeks fell in survival group. The serum level of ET-1 measured by EIA method were compared between thepatients with different severity of lung injury [ evaluated by American-European Consensus Conference on ARDS ( AECC) criteria and lung injury score( LIS) ] , and between the patients with different prognosis ( death or survival ) . The correlation was analyzed between the level of ET-1 and clinical parameters.Results The ET-1 level was higher in the ALI/ARDS patients than that in the control subjects [ ( 6. 18 ±4. 48) ng/L vs. ( 2. 68 ±1. 34) ng/L, P lt;0. 05] . There was no significant difference in the patients with different severity [ ALI vs. ARDS, ( 5. 43 ±4. 39) ng/L vs. ( 7. 01 ±4. 51) ng/L, P gt; 0. 05; LIS≤2. 5 vs.LISgt;2. 5, ( 5. 93 ±5. 21) ng/L vs. ( 6. 68 ±2. 76) ng/L, P gt; 0. 05] . The ET-1 level in the death group continued to increase, and higher than that in the survival group on the 5th day [ ( 7. 96 ±3. 30) ng/L vs.( 4. 36 ±3. 29) ng/L, P lt; 0. 05] . The ET-1 level was positively correlated with SIRS, SAPSⅡ and APACHEⅡ ( r = 0. 359, 0. 369 and 0. 426, respectively, P lt; 0. 05 ) , and negatively correlated with PaO2 /FiO2 and AaDO2 ( r = - 0. 286 and - 0. 300, respectively, P lt;0. 05) . Conclusion The measurementof serum ET-1 can help to evaluate the severity and prognosis of ALI/ARDS patients.
Objective To observe the effects of penehyclidine hydrochloride ( PHCD) combined with mechanical ventilation ( MV) on inflammatory response in rats with ARDS induced by oleic acid ( OA) .Methods The rat ARDS model was established by OA via intravenous injection ( iv) . 32 adult healthy male SD rats were randomly divided into four groups, ie. a normal control group( group C: intra-peritoneal injection of a same amount of normal saline and intravenous injection of a same amount of normal saline respectively rather than PHCD) , a model group( group A1) , a PHCD group ( group A2: intra-peritoneal injection of 0. 5 mg/kg PHCD30 minutes before OA iv) and a PHCD+MV group ( group A3: VT = 4 mL/kg,respiratory rate =70 beats /min, I∶E =1∶2, FiO2 =21%) . Four hours after OA iv, arterial partial pressure of oxygen ( PaO2 ) was measured, and the oxygenation index ( PaO2 /FiO2 ) as well as wet /dry weight ratio( W/D) of lung tissue were calculated respectively. The pathological changes of lung tissue was observed through light microspcope. Interlukin-8 ( IL-8 ) , myeloperoxidase ( MPO) and NF-κB in lung tissue homogenate were measured by enzyme linked immunosorbent assay ( ELISA ) . Results Extensive pneumonedema, pneumorrhagia, focal atelectasis and amout of inflammatory cells infiltration in lung tissues were all revealed in ARDS rats. Lung injury score ( 8. 63 ±2. 20 vs. 1. 38 ±0. 92) , W/D ratio ( 8. 37 ±0. 99 vs. 4. 08 ±0. 65) were all higher in the ARDS rats than those in group C( all P lt;0. 01) . PaO2 /FiO2 was lower in group A1 than that in group C [ ( 206 ±32) mm Hg vs. ( 428 ±28) mm Hg, P lt; 0. 01] . The concentrations of MPO [ ( 33. 91 ±1. 43) ng/mL vs. ( 20. 92 ±1. 40) ng/mL) ] , IL-8 [ ( 809 ±39) ng/L vs. ( 583 ±91) ng/L] and NF-κB [ ( 1163 ±105) ng/L vs. ( 803 ±130) ng/L] in lung tissue homogenate were significantly increased in the ARDS rats than those in group C ( all P lt;0. 01) . Pathological changes of lung tissue ( including pneumonedema, pneumorrhagia, atelectasis and inflammatory cell infiltration, etc. )obviously improved when treated by PHCD or/and PHCD combined with MV ( all P lt;0. 05) . PaO2 /FiO2 in group A2 and A3 were both significantly increased when compared with group A1 ( both P lt; 0. 05) .Meanwhile,W/D ratio, lung injury score, and concentrations of MOP, IL-8 and NF-κB were sharply decreased in group A2 and A3 ( all P lt;0. 05) . The improvement in all above indices were more significant in group A3 than those in group A2, despite all those indices failed to meet the levels of normal rats ( all P lt; 0. 05) .Conclusion PHCD can inhibit the inflammatory response in ARDS rats induced by OA iv, through which it protect the lung tissue frominjury induced by OA. The protective role of PHCD plus MV is superior to that of PHCD only.
ObjectiveTo establish paraquat (PQ)-induced acute respiratory distress syndrome (ARDS) mice model via gavage, in order to simulate oral adminitration in clinical situations.MethodsSeventy-eight 6-8-week-old, specific pathogen free female C57 mice were chosen in this study. The mice were randomly divided into the control group (n=6) and the PQ model group(n=36); the mice in the latter group were randomly divided into 6 poisoning model subgroups further, with 6 mice in each, to find out the suitable concentration of PQ to establish stable ARDS model. The mice in the control group were given phosphatebuffer saline (PBS) by gavage, 200 μL per mouse; while the mice in the 6 poisoning model subgroups were given PQ with varies doses of 3, 10, 30, 100, 150, 300 mg/kg respectively by gavage. The clinical manifestations were observed for 7 days, and the ratio of lung wet/dry (W/D) was measured. After the suitable concentration of PQ for stable ARDS mice model was found, the other 36 mice were randomly divided into the controlgroup and the poisoning model group, both were divided into 4 subgroups, according to different observation point in time (1 day and 2, 3, 4 days after PQ gavage). The mice in the 4 control subgroups (n=3) were given PBS by gavage, 200 μL per mouse; while the mice in the 4 poisoning model subgroups (n=6) were given PQ with the suitable concentration for ARDS mice model by gavage. Pathological manifestations by Haematoxylin-Eosin staining and lung injury score were observed and analyzed.ResultsThe mice began to die at the PQ dosage of 150 mg/kg; while the death rate was stable at 300 mg/kg. On the 2nd and 4th day after PQ gavage, lung W/D was 5.335, 6.113, and 5.525, and 6.403, respectively in the mice in 150 and 300 mg/kg subgroup, which differed much from those in the control group (P<0.001). Congestion, edema, hemorrhage, alveolar structure damage, inflammation cells infiltration of lung tissue were observed, and lung injury score increased.ConclusionPQ-induced ARDS mice model by gavage is established successfully.
Objective To observe the level of vascular endothelium growth factor A( VEGF-A) in exhaled breath condensate ( EBC) of patients with acute lung injury/acute respiratory distress syndrome ( ALI/ARDS) , and investigate its clinical significance. Methods EBC of 23 patients with ALI/ARDS by mechanical ventilation in intensive care unit ( ICU) were collected with improved EcoScreen condenser. EBC of 17 normal control subjects were collected with EcoScreen condensor. The level of VEGF-A was measured by ELISA in EBC and serum. The levels of VEGF-A in EBC of patients with different grades of lung injuries were compared, and the correlation was analyzed between the level of VEGF-A and clinical indicators. Results The level of VEGF-A in EBC was lower in the patients with ALI/ARDS than that of control subjects [ ( 49. 88 ±6. 32) ng/L vs. ( 56. 50 ±6. 323) ng/L, P lt;0. 01] , the level of VEGF-A was higher in the ALI patients than that of ARDS patients [ ( 53. 56 ±5. 56) ng/L vs. ( 45. 86 ±4. 45) ng/L, P lt;0. 01] ,and higher in the survival patients than that of the died patients [ ( 51. 92 ±6. 28) ng/L vs. ( 46. 05 ± 4. 58) ng/L, P lt;0. 05] . The level of VEGF-A in EBC was negatively correlated with lung injury score and A-aDO2 /PaO2 ( r = - 0. 426 and - 0. 510, respectively, P lt;0. 05) , and positively correlated with PaO2 /FiO2 and PaO2 ( r =0. 626 and 0. 655, respectively, P lt; 0. 05) . The level of VEGF-A in serum was not different between the ALI/ARDS patients and the control subjects, between the ALI and ARDS patients, or between the survival and the died patients ( all P gt;0. 05) . The level of VEGF-A in serumhad no correlation with lung injury score, A-aDO2 /PaO2 , PaO2 /FiO2 , or PaO2 ( all P gt;0. 05) . Conclusion The changes of VEGF-A in EBC of patients with ALI/ARDSmay serve as an indicator for severity and prognosis evaluation.
Objective To explore the role of renin-angiotensin system( RAS) in acute lung injury( ALI) /acute respiratory dysfunction syndrome( ARDS) by using amouse cecal ligation and puncture ( CLP)model.Methods The ALI/ARDS animal models were assessed bymeasuring blood gas, wet/dry lung weight ratio( W/D) , and lung tissue histology 18 hours after CLP operation. After the ALI/ARDS models was successfully established, immunohistochemistry, western blotting and radioimmunity were used to investigate the changes of several key enzymes of RAS, such as ACE, ACE2 and Ang Ⅱ. In addition, two groups of animals received a separate intraperitoneal injection of angiotensin-converting enzyme ( ACE) inhibitor captopril or recombinant mouse ACE2 ( rmACE2) after CLP, then the changes of RAS in ALI/ARDS modelswere observed. Results The extensive lung injuries can be observed in the lung tissues from CLP-treated animals 18 hours after operation. The CLP-induced ALI/ARDS led to an increase in the wet/dry weight ratio of the lung tissues, and a decrease in the PaO2 /FiO2 [ ( 194. 3 ±23. 9) mm Hg vs ( 346. 7 ±20. 5) mm Hg,P lt;0. 01] . Immunohistochemistry and western blotting tests of the lung tissues from CLP-treated animals showed a decrease in the ACE2 protein level. However, in both the CLP and sham mice there were no significant differences between the two groups. CLP markedly increased Ang Ⅱ level in lungs and plasma of mice, and RAS drugs significantly impacted the Ang Ⅱ levels of mice. Compared with the CLP group,captopril or rmACE2 led to a decrease of the Ang Ⅱ level in mice [ Lung: ( 1. 58 ±0. 16) fmol /mg,( 1. 65 ±0. 21) fmol /mg vs ( 2. 38 ±0. 41) fmol /mg; Plasma: ( 178. 04 ±17. 87) fmol /mL, ( 153. 74 ±10. 24) fmol /mL vs ( 213. 38 ± 25. 44) fmol /mL] . Conclusions RAS activation is one of the characteristics of CLP-induced ALI/ARDS in mice models. ACE and ACE2 in RAS have a different role in the regulation of AngⅡ synthesis, while ACE has a positive effect in generating AngⅡ, and ACE2 shows a negative effect.
ObjectiveTo evaluate systematically the relationship between obesity and clinical prognosis in acute respiratory distress syndrome (ARDS) patients.MethodsA systematic search was performed in Pubmed, EMBASE, Cochrane databases, Wiley, Ovid, Medline, CNKI, VIP and Wanfang. All studies that reported obesity in the clinical prognosis of ARDS and acute lung injury were included. A meta-analysis was performed using RevMan 5.0 and Stata 10.0.ResultsA total of 28 368 patients from 9 studies were included in this meta-analysis. The combined results showed that obesity was associated with the decreased mortality of ARDS [odds ratio(OR)=0.63, 95% confidence intervals (95%CI) 0.41 to 0.98, P=0.04]. In subgroup analysis, the result showed no obvious relationship between obesity and 28-day mortality in ARDS/ALI (OR=0.92, 95%CI 0.55 to 1.54, P=0.76). However, obesity was associated with lower risk of 60days and 90-day mortality in ARDS/ALI (60-day: OR=0.84, 95%CI 0.75 to 0.94, P=0.002; 90-day: OR=0.38, 95%CI 0.22 to 0.66, P=0.000 5). Compared with normal weight patients with ARDS, hospital length of stay, ICU length of stay, and duration of mechanical ventilation did not differ significantly [hospital length of stay: weighted mean difference (WMD)=3.61, 95%CI –0.36 to 7.57, P=0.07; intensive care unit (ICU) length of stay: WMD=1.52, 95%CI –0.22 to 3.26, P=0.09; duration of mechanical ventilation: WMD=–0.50, 95%CI –2.18 to 1.19, P=0.56], but ventilator-free days was significantly longer in obese patients (WMD=2.68, 95%CI 0.86 to 4.51, P=0.004).ConclusionsObesity is not associated with hospital length of stay, ICU length of stay, and duration of mechanical ventilation in patients with ARDS. However, obesity is associated with a reduction of long-term mortality and increased ventilator-free days in the patients with ARDS. Additional larger randomized controlled studies are needed to confirm the possible role of obesity in the clinical prognosis of ARDS.
ObjectiveTo improve clinicians' understanding of severe cytokine release syndrome (CRS) through reporting the clinical manifestation, diagnosis, treatment, and prognosis of CRS after chimeric antigen receptor T (CAR-T) cell therapy in a patient with solid tumor. Methods A patient with ovarian cancer who suffered severe CRS after CAR-T cell therapy in the Department of Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University was reviewed. Relevant studies were searched for literature review. Results The patient, a 55-year-old woman, was diagnosed with ovarian cancer in early 2016 and continued to progress despite multiple lines of treatment, so she received CAR-T cell therapy on September 16, 2022. The patient developed a fever 2 days after infusion, and developed dyspnea and shortness of breath with oxygen desaturation 2 days later. Her condition kept deteriorating with respiratory distress and severe hypoxia 6 days after infusion, and the level of interleukin-6 and interferon-gamma continued to be elevated. Chest CT showed pleural effusion and massive exudation of both lungs. Considered to have acute respiratory distress syndrome (ARDS) due to severe CRS, she was transferred to the intensive care unit (ICU). The patient was treated with tocilizumab, high-dose intravenous glucocorticoid pulses, mechanical ventilation, and sivelestat sodium for ARDS. Her symptoms were gradually relieved, and the results of laboratory tests were gradually stabilized. The patient was extubated 6 days after ICU admission and discharged from ICU a week later. Six patients were screened out with ARDS or acute respiratory failure caused by CRS after CAR-T cell therapy, whose treatments were mainly anticytokine agents combined with high-flow oxygen therapy or invasive mechanical ventilation. One of them died. ConclusionsClinicians should be alert to severe CRS during the administration of CAR-T cell. Rapid interruption of the inflammation development is the key to all treatments. If respiratory and/or circulatory dysfunction occurs, patients should be transferred to ICU in time for organ support therapy.
Objective To explore clinical significance of interleukin-8 (IL-8), clarada protein 16 (CC16), and intercellular adhesion molecule-1 (ICAM-1) in exhaled breath condensate (EBC) and serum samples collected from patients with acute respiratory distress syndrome (ARDS). Methods A total of 45 ARDS patients were assigned into a mild ARDS group (n=20), a moderate ARDS group (n=15) and a severe ARDS group (n=10) based on the Berlin definition. During the same study period, 45 healthy subjects were recruited as control. Serum and EBC levels of IL-8, CC16 and ICAM-1 were detected on the first and fifth day of admission. Results Compared with the control group, serum and EBC IL-8, CC16 and ICAM-1 were significantly higher in the ARDS groups (P<0.05). Serum and EBC IL-8 levels increased with the severity of ARDS, whereas no significant difference was detected between the three groups (P>0.05). Compared with the mild group and the moderate group, serum and EBC CC16 levels were significantly higher in the severe ARDS group. At the first day after admission, serum ICAM-1 was higher in the severe and moderate ARDS groups than that in the mild ARDS group (P<0.05). Meanwhile, EBC ICAM-1 was significantly different between the three groups (P<0.05). At the fifth day after admission, different EBC ICAM-1 was identified between the severe ARDS group and the other two groups (P<0.05). Regardless of ARDS severity, there were no significant differences in serum and EBC IL-8 and CC16 levels at the first and fifth days after admission (P>0.05). However, serum and EBC ICAM-1 at the first and fifth days showed significant difference (except in the mild ARDS group) (P<0.05). The levels of ICAM-1 in serum and EBC of death group were significantly higher than those of survival group (P<0.05). Conclusion Serum and EBC IL-8, CC16 and ICAM-1 are of significance in diagnosis and prognosis evaluation of ARDS.
