Risk Factor For ARDS Research Articles

Electronic health record biobank cohort recapitulates an association between the MUC5B promoter polymorphism and ARDS in critically ill adults.

Large population-based DNA biobanks linked to electronic health records (EHRs) may provide novel opportunities to identify genetic drivers of ARDS. Can we develop an EHR-based algorithm to identify ARDS in a biobank database, and can this validate a previously reported ARDS genetic risk factor? We analyzed two parallel genotyped cohorts: a prospective biomarker cohort of critically ill adults (VALID), and a retrospective cohort of hospitalized participants enrolled in a de-identified EHR biobank (BioVU). ARDS was identified by clinician-investigator review in VALID and an EHR algorithm in BioVU (EHR-ARDS). We tested the association between the MUC5B promoter polymorphism rs35705950 with development of ARDS, and assessed if age modified this genetic association in each cohort. In VALID, 2,795 patients were included, age was 55 [43, 66] (median [IQR]) years, and 718 (25.7%) developed ARDS. In BioVU, 9,025 hospitalized participants were included, age was 60 [48, 70] years, and 1,056 (11.7%) developed EHR-ARDS. We observed a significant age-related interaction effect on ARDS in VALID: among older patients, rs35705950 was associated with increased ARDS risk (OR: 1.44; 95%CI 1.08-1.92; p=0.012) whereas among younger patients this effect was absent (OR: 0.84; 95%CI: 0.62-1.14; p=0.26). In BioVU, rs35705950 was associated with increased risk for EHR-ARDS among all participants (OR: 1.20; 95%CI: 1.00-1.43, p=0.043) and this did not vary by age. The polymorphism was also associated worse oxygenation in mechanically ventilated BioVU participants, but had no association with oxygenation in VALID. The MUC5B promoter polymorphism was associated with ARDS in two cohorts of at-risk adults. Although age-related effect modification was observed only in VALID, BioVU identified a consistent association between MUC5B and ARDS risk regardless of age, and a novel association with oxygenation impairment. Our study highlights the potential for EHR biobanks to enable precision-medicine ARDS studies.

Risk factors for acute respiratory distress syndrome in sepsis patients: A meta-analysis

BackgroundAcute Respiratory Distress Syndrome (ARDS) is a critical complication of sepsis, associated with high morbidity and mortality. Identifying risk factors for ARDS among sepsis patients is essential for early intervention and improving outcomes. MethodsWe conducted a comprehensive meta-analysis, reviewing studies that examined the association between various risk factors and ARDS development in sepsis patients. Databases such as PubMed, EMBASE, Cochrane Library, Medline, CINAHL, and Web of Science were searched up to January 2024, without language restrictions. Eligible studies included observational cohorts and case-control studies. Pooled odds ratios (ORs) and standardized mean differences (SMDs) were calculated using a random-effects model. Heterogeneity was assessed through I2 statistics, and publication bias was evaluated via the Luis Furuya-Kanamori (LFK) index. Results15 studies with more than 40,000 participants were analyzed. Significant risk factors for ARDS included pulmonary infection (OR: 2.696, 95 % CI: 1.655 to 4.390), septic shock (OR: 2.627, 95 % CI: 1.850 to 3.731), and pancreatitis (OR: 3.734, 95 % CI: 2.958 to 4.712). No significant associations were found between the development of ARDS in septic patients and the following risk factors: sex (OR: 1.106, 95%CI: 0.957–1.279), smoking status (OR: 1.214, 95%CI: 0.835–1.765), or steroid use (OR: 0.901, 95%CI: 0.617–1.314). APACHE-II and SOFA scores were predictive of ARDS development, emphasizing their utility in clinical assessments. ConclusionPulmonary infection, septic shock, and pancreatitis significantly increase ARDS risk in sepsis patients. Our findings advocate for targeted management of these risk factors to mitigate ARDS development, emphasizing the importance of personalized care in sepsis management.

High incidence of adult respiratory distress syndrome associated with amphetamine use in the burn population: a retrospective cohort study.

A total of 188 patients age 18 and older with total body surface area (TBSA) between 20 and 60% were sampled over 5 years. To capture the moderate to severe burn population, a lower limit of 20% was chosen while 60% was used as the upper limit to exclude patients likely to die from the burns alone. Patients eligible to be include in the study had to meet the TBSA criteria. Demographic data was ascertained. Patients were placed into two cohorts: the amphetamine positive group (AmPOS), the amphetamine negative group (AmNEG). Key endpoints included hospital mortality, length of ICU stay, development of ARDS, and cardiac output parameters. Nonparametric data was evaluated with the Mann-Whitney test and categorical variables were compared using χ 2. Data from 49 patients with ARDS were collected retrospectively out of the 188 patients in this TBSA range. The incidence of amphetamine abuse in these burn patients is 14.9%. The average age of AmPOS and AmNEG patients was 36 and 34 and the average TBSA of burns in the AmPOS and AmNEG group was 51.8 and 45.2%. The mean onset of ARDS was 2.2 days for the AmPOS versus 3.3 days for the AmNEG (P=0.19). At admission, patients with amphetamine use exhibited less inhalational injury and a lower Acute Physiology and Chronic Health Evaluation II (APACHE II) score. In AmPOS, 64% developed ARDS compared to 19% in AmNEG (P<0.001). Mortality, time on a ventilator, ICU days, packed Red Blood Cell, Fresh Frozen Plasm, platelets transfused, and initial cardiac parameters all were not statistically significant. On the initial date of ARDS diagnosis, there was no statistically significant difference with PaO2/FiO2 and compliance (P=0.67), but positive end expiratory pressure requirements was higher in AmPOS (P=0.018). Amphetamine Use was associated with increased risk of developing ARDS in the burn population. This is despite having a better APACHE II and lower incidence of inhalational injury in the AmPOS group, supporting amphetamine as an independent risk factor for ARDS.

Alcohol use disorder as a potential risk factor for COVID-19 severity: A narrative review.

In Dec. 2019-January 2020, a pneumonia illness originating in Wuhan, China, designated as coronavirus disease 2019 (COVID-19) was shown to be caused by a novel RNA coronavirus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). People with advanced age, male sex, and/or underlying health conditions (obesity, type 2 diabetes, cardiovascular disease, hypertension, chronic kidney disease, and chronic lung disease) are especially vulnerable to severe COVID-19 symptoms and death. These risk factors impact the immune system and are also associated with poor health, chronic illness, and shortened longevity. However, a large percent of patients without these known risk factors also develops severe COVID-19 disease that can result in death. Thus, there must exist risk factors that promote exaggerated inflammatory and immune response to the SARS-CoV-2 virus leading to death. One such risk factor may be alcohol misuse and alcohol use disorder because these can exacerbate viral lung infections like SARS, influenza, and pneumonia. Thus, it is highly plausible that alcohol misuse is a risk factor for either increased infection rate when individuals are exposed to SARS-CoV-2 virus and/or more severe COVID-19 in infected patients. Alcohol use is a well-known risk factor for lung diseases and ARDS in SARS patients. We propose that alcohol has three key pathogenic elements in common with other COVID-19 severity risk factors: namely, inflammatory microbiota dysbiosis, leaky gut, and systemic activation of the NLRP3 inflammasome. We also propose that these three elements represent targets for therapy for severe COVID-19.

Post-Transplant and In-Hospital Risk Factors for ARDS After Hematopoietic Stem Cell Transplantation.

ARDS is a serious complication of hematopoietic stem cell transplant (HSCT). Pre-transplant risk factors for developing ARDS after HSCT have been recently identified. The objective of this study was to better understand post-transplant risk factors for developing ARDS after HSCT. This was a nested case-control study. ARDS cases were matched to hospitalized non-ARDS controls by age, type of transplantation (allogeneic vs autologous), and time from transplantation. In a conditional logistic regression model, any potential risk factors were adjusted a priori for risk factors known to be associated with ARDS development. One hundred and seventy ARDS cases were matched 1:1 to non-ARDS hospitalized controls. Pre-admission, cases were more likely to be on steroids (odds ratio [OR] 1.90 [1.13-3.19], P = .02). At time of admission, cases had lower platelet count (OR 0.95 [0.91-0.99], P = .02), lower bicarbonate (OR 0.94 [0.88-0.99], P = .035), and higher creatinine (OR 1.91 [1.23-2.94], P = .004). During the first 24 h after admission, cases were more likely to have received transfusion (OR 2.41 [1.48-3.94], P < .001), opioids (OR 2.94 [1.67-5.18], P < .001), and have greater fluid administration (OR 1.52 [1.30-1.78], P < .001). During the hospitalization, ARDS cases had higher temperature (OR 1.77 [1.34-2.33], P < .001) and higher breathing frequency (OR 1.52 [1.33-1.74], P < .001). ARDS cases were more likely to have had sepsis (OR 68.0 [15.2-301.7], P < .001), bloodstream infection (OR 4.59 [2.46-8.57], P < .001), and pneumonia (OR 9.76 [5.01-19.00], P < .001). Several post-transplant predictors of ARDS development specific to the HSCT population were identified in the pre-hospital and early in-hospital domains. These findings can provide insights into causal mechanisms of ARDS development and be used to develop HSCT-specific risk prediction models.

Impact of age, sex, race, and regionality on major clinical outcomes of COVID-19 in hospitalized patients in the United States

BackgroundThe COVID-19 pandemic has affected all people across the globe. Regional and community differences in timing and severity of surges throughout the pandemic can provide insight into risk factors for worse outcomes in those hospitalized with COVID-19.MethodsThe study cohort was derived from the Cerner Real World Data (CRWD) COVID-19 Database made up of hospitalized patients with proven infection from December 1, 2019 through November 30, 2020. Baseline demographic information, comorbidities, and hospital characteristics were obtained. We performed multivariate analysis to determine if age, race, comorbidity and regionality were predictors for mortality, ARDS, mechanical ventilation or sepsis hospitalized patients with COVID-19.ResultsOf 100,902 hospitalized COVID-19 patients included in the analysis (median age 52 years, IQR 36–67; 50.7% female), COVID-19 case fatality rate was 8.5% with majority of deaths in those ≥ 65 years (70.8%). In multivariate analysis, age ≥ 65 years, male gender and higher Charlson Comorbidity Index (CCI) were independent risk factors for mortality and ARDS. Those identifying as non-Black or non-White race have a marginally higher risk for mortality (OR 1.101, CI 1.032–1.174) and greater risk of ARDS (OR 1.44, CI 1.334–1.554) when compared to those who identify as White. The risk of mortality or ARDS was similar for Blacks as Whites. Multivariate analysis found higher mortality risk in the Northeast (OR 1.299, CI 1.22–1.29) and West (OR 1.26, CI 1.18–1.34). Larger hospitals also had an increased risk of mortality, greatest in hospitals with 500–999 beds (OR 1.67, CI 1.43–1.95).ConclusionAdvanced age, male sex and a higher CCI predicted worse outcomes in hospitalized COVID-19 patients. In multivariate analysis, worse outcomes were identified in small minority populations, however there was no difference in study outcomes between those who identify as Black or White.

Acute respiratory distress syndrome after in-hospital cardiac arrest

ObjectiveAcute respiratory distress syndrome (ARDS) after out-of-hospital cardiac arrest is common and associated with worse outcomes. In the hospital setting, there are many potential risk factors for post-arrest ARDS, such as aspiration, sepsis, and shock. ARDS after in-hospital cardiac arrest (IHCA) has not been characterized. MethodsWe performed a single-center retrospective study of adult patients admitted to the hospital between 2014–2018 who suffered an IHCA, achieved return of spontaneous circulation (ROSC), and were either already intubated at the time of arrest or within 2 hours of ROSC. Post-IHCA ARDS was defined as meeting the Berlin criteria in the first 3 days following ROSC. Outcomes included alive-and-ventilator free days across 28 days, hospital length-of-stay, hospital mortality, and hospital disposition. ResultsOf 203 patients included, 146 (71.9%) developed ARDS. In unadjusted analysis, patients with ARDS had fewer alive-and-ventilator-free days over 28 days with a median of 1 (IQR: 0, 21) day, compared to 18 (IQR: 0, 25) days in patients without ARDS (p = 0.03). However, this association was not significant after multivariate adjustment. There was also a non-significant longer hospital length-of-stay (15 [IQR: 7, 26] vs 10 [IQR: 7, 22] days, p = 0.25; median adjusted increase in ARDS patients: 3 [95% CI: −2 to 8] days, p = 0.27) and higher hospital mortality (53% vs 44%, p = 0.26; aOR 1.6 [95% CI: 0.8–2.9], p = 0.17) in the ARDS group. ConclusionAmong IHCA patients, almost three-quarters developed ARDS within 3 days of ROSC. As in out of hospital cardiac arrest, post-IHCA ARDS is common.

A novel biomarker for bacteremia in acute pyelonephritis during pregnancy

Sepsis is a leading cause of maternal death and its diagnosis during the golden hour is critical to improve survival. Acute pyelonephritis, a leading cause of sepsis, is a risk factor for ARDS, renal failure, and DIC. Bacteremia occurs in 15-20% of pregnant patients with pyelonephritis and its recognition depends on the availability of cultures, which takes time. A test for the rapid detection of blood-borne infections is needed. Soluble suppression of tumorigenicity 2 (sST2) has been proposed as a biomarker for sepsis in adults and children (GREAT Network, Ann Lab Med, 2015).

Fluid resuscitation based on pulse contour cardiac output monitoring is associated with improved prognosis in adult severe burn patients: a retrospective cohort study.

A monitoring method is needed to further guide fluid resuscitation in severe burn injury. This study was performed to investigate the effects of pulse contour cardiac output (PCCO) monitoring on the prognosis of adult severe burns patients. We conducted a retrospective study enrolling patients from January 2015 to December 2020, who were divided into a control group receiving conventional monitoring and a study group receiving PCCO monitoring. The primary outcomes were 28-day mortality and total mortality, and the secondary outcomes included burn-related complications and the length of hospital stay and ICU stay. Multivariable logistic regression analysis and linear regression analysis were performed to determine the risk factors of burns-related complications and length of hospital stay in enrolled patients. A total of 109 patients in the control group and 82 patients in the study group were enrolled. While the area of full thickness burn was much higher in the control group than in the study group (P=0.021), no significant difference was found in other characteristics between the two groups. During fluid resuscitation, the fluid volume ratio of the study group was significantly different from that of the control group, and both in the first 24 hours and the second 24 hours, the resuscitation fluid volume ratio and colloid volume ratio was significantly higher in the control group than in the study group (all P<0.001). Eight patients died during treatment, and there were more patients experiencing AKI and ARDS in the control group than in the study group (P=0.029 and 0.016). The lengths of hospital stay and ICU stay in the study group was much shorter than in the control group (P<0.001 and 0.005). In addition, TBSA was an important risk factor for both AKI and ARDS, and the existence of inhalation injury and older age increased the incidence of ARDS. Higher TBSA, inhalation injury, and burn-related complications were related to longer hospital stay in enrolled patients. Fluid resuscitation according to PCCO monitoring can effectively reduce the volume of colloid and overall fluid volume and reduce the incidence of burns-related complications and shorten the length of hospital stay.

Driving Pressure Is a Risk Factor for ARDS in Mechanically Ventilated Subjects Without ARDS.

Driving pressure (ΔP) has been described as a risk factor for mortality in patients with ARDS. However, the role of ΔP in the outcome of patients without ARDS and on mechanical ventilation has received less attention. Our objective was to evaluate the association between ΔP on the first day of mechanical ventilation with the development of ARDS. This was a post hoc analysis of a multicenter, prospective, observational, international study that included subjects who were on mechanical ventilation for > 12 h. Our objective was to evaluate the association between ΔP on the first day of mechanical ventilation with the development of ARDS. To assess the effect of ΔP, a logistic regression analysis was performed when adjusting for other potential risk factors. Validation of the results obtained was performed by using a bootstrap method and by repeating the same analyses at day 2. A total of 1,575 subjects were included, of whom 65 (4.1%) developed ARDS. The ΔP was independently associated with ARDS (odds ratio [OR] 1.12, 95% CI 1.07-1.18 for each cm H2O of ΔP increase, P < .001). The same results were observed at day 2 (OR 1.14, 95% CI 1.07-1.21; P < .001) and after bootstrap validation (OR 1.13, 95% CI 1.04-1.22; P < .001). When taking the prevalence of ARDS in the lowest quartile of ΔP (≤9 cm H2O) as a reference, the subjects with ΔP > 12-15 cm H2O and those with ΔP > 15 cm H2O presented a higher probability of ARDS (OR 3.65, 95% CI 1.32-10.04 [P = .01] and OR 7.31, 95% CI, 2.89-18.50 [P < .001], respectively). In the subjects without ARDS, a higher level of ΔP on the first day of mechanical ventilation was associated with later development of ARDS. (ClinicalTrials.gov registration NCT02731898.).

Death in hospital following ICU discharge: insights from the LUNG SAFE study

BackgroundTo determine the frequency of, and factors associated with, death in hospital following ICU discharge to the ward.MethodsThe Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE study was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted across 459 ICUs from 50 countries globally. This study aimed to understand the frequency and factors associated with death in hospital in patients who survived their ICU stay. We examined outcomes in the subpopulation discharged with no limitations of life sustaining treatments (‘treatment limitations’), and the subpopulations with treatment limitations.Results2186 (94%) patients with no treatment limitations discharged from ICU survived, while 142 (6%) died in hospital. 118 (61%) of patients with treatment limitations survived while 77 (39%) patients died in hospital. Patients without treatment limitations that died in hospital after ICU discharge were older, more likely to have COPD, immunocompromise or chronic renal failure, less likely to have trauma as a risk factor for ARDS. Patients that died post ICU discharge were less likely to receive neuromuscular blockade, or to receive any adjunctive measure, and had a higher pre- ICU discharge non-pulmonary SOFA score. A similar pattern was seen in patients with treatment limitations that died in hospital following ICU discharge.ConclusionsA significant proportion of patients die in hospital following discharge from ICU, with higher mortality in patients with limitations of life-sustaining treatments in place. Non-survivors had higher systemic illness severity scores at ICU discharge than survivors.Trial Registration: ClinicalTrials.gov NCT02010073.

RBC transfusion is associated with increased risk of respiratory failure after pneumonectomy.

Pneumonectomy is associated with high risk of respiratory complications. Our objective was to determine if transfusions are associated with increased rate of ARDS and respiratory failure in adults undergoing elective pneumonectomy. Retrospective cohort study of consecutive pneumonectomies undertaken at a tertiary hospital (2003-2013). Multivariable logistic regression was performed to adjust for confounding factors. ARDS and respiratory failure occurred in 12.4% (n = 20) and 19.2% (n = 31) of 161 pneumonectomy patients, respectively, and were more likely to occur in transfused patients (P = 0.03, P < 0.001). pRBCs, FFP and platelets were transfused in 27% (n = 43), 6% (n = 9), and 2% (n = 3), respectively. On multivariable analyses utilizing blood products as continuous and binary variables, pRBC use was the only independent predictor of ARDS with odds ratio (OR) = 1.23 (95%CI:1.08-1.39, P = 0.002) and OR = 2.45 (95%CI:1.10-5.49, P = 0.03), respectively. On multivariable analyses utilizing blood products as continuous and binary variables, pRBCs were the only independent predictor of respiratory failure with OR = 1.37 (95%CI:1.16-1.60, P < 0.001) and OR = 3.17 (95%CI:1.25-8.02, P = 0.02), respectively. Peri-operative pRBC use appears to be an independent risk factor for ARDS and respiratory failure after pneumonectomy. There is a significant dose-response relationship. Platelets and FFP did not appear to increase ARDS risk but this may be due to low utilization.

Acute respiratory distress syndrome after orthotopic liver transplantation

PurposeAcute respiratory distress syndrome (ARDS) is a devastating complication with substantial mortality. The aims of this study were to identify the incidence, preoperative and intraoperative risk factors, and impact of ARDS on outcomes in patients after orthotopic liver transplantation (OLT). Materials and methodsAdult OLT patients between January 2004 and October 2013 at our center were included. Postoperative ARDS was determined using the criteria proposed by the Berlin Definition. Multivariate logistic models were used to identify preoperative and intraoperative risk factors for ARDS. ResultsOf 1726 patients during the study period, 71 (4.1%) developed ARDS. In the preoperative model, encephalopathy (odds ratio [OR], 2.22; P = .022), preoperative requirement of intubation (OR, 2.06; P = .020), and total bilirubin (OR, 1.02; P = .003) were independent risk factors. In the intraoperative model, large pressor bolus was the sole risk factor for ARDS (OR, 2.69; P = .001). Postoperatively, patients with ARDS had a 2-fold increase in 1-year mortality, mechanical ventilation time, and length of hospital stay. ConclusionsAcute respiratory distress syndrome occurred at a rate of 4.1% following OLT in adult patients and was associated with preoperative encephalopathy, requirement of intubation, and total bilirubin and intraoperative large boluses of pressors. Acute respiratory distress syndrome was associated with increased mortality, longer ventilation time, and hospital stay.

Which Patients With ARDS Benefit From Lung Biopsy?

A central tenet of caring for patients with ARDS is to treat the underlying cause, be it sepsis, pneumonia, or removal of an offending toxin. Identifying the risk factor for ARDS has even been proposed as essential to diagnosing ARDS. Not infrequently, however, the precipitant for acute hypoxemic respiratory failure is unclear, and this raises the question of whether a histologic lung diagnosis would benefit the patient. In this review, we consider the historic role of pathology in establishing a diagnosis of ARDS and the published experience of surgical and transbronchial lung biopsy in patients with ARDS. We reflect on which pathologic diagnoses influence treatment and suggest a patient-centric approach to weigh the risks and benefits of a lung biopsy for critically ill patients who may have ARDS.

Drug-Associated Acute Lung Injury: A Population-Based Cohort Study

A number of drugs have been reported as risk factors for acute lung injury (ALI) and ARDS. However, evidence is largely limited to case reports, and there is a paucity of data on the incidence and outcome of drug-associated ALI (DALI). Using a population-based retrospective cohort study design, critically ill patients with a diagnosis of ALI were studied. These patients were classified as having DALI or non-DALI, based on whether they were exposed to prespecified drugs prior to development of ALI. Outcomes were compared between the two groups and frequencies and incidences reported. Among 514 patients with ALI, 49 (9.5%) had DALI with an estimated population-based incidence of 6.6 (95% CI, 4.8-8.5) per 100,000 person-years. Of the 49 patients with DALI,36 received chemotherapeutic/antiinflammatory agents, and 14 received amiodarone. Twelve patients had no additional risk factors for ALI (probable DALI), whereas 37 had alternative risk factors (possible DALI). Patients with and without DALI had similar baseline characteristics. However, the APACHE (Acute Physiology and Chronic Health Evaluation) III scores (median, 83 vs 70, P 5 .03), ICU mortality (35% vs 20%, P 5 .03), and hospital mortality (63% vs 32%, P , .001)were significantly higher in the DALI group compared with those of the non-DALI group. Hospital mortality remained significantly higher after adjusting for APACHE III score on admission and the presence of malignancy in logistic regression analysis (OR, 2.8; 95% CI, 1.3-6.4; P 5 .009). Drugs are important risk factors for ALI, and recognizing them as such may have important implications for early identification of patients at risk, discontinuation of the offending agent, and prognosis.

Lower incidence of acute respiratory distress syndrome in community‐acquired pneumonia patients aged 85 years or older

Clinical variables and laboratory data were compared to elucidate the risk factors associated with the development of ARDS among elderly patients with community-acquired pneumonia (CAP). The predictors for ARDS appeared to differ from the determinants of severity of CAP. ARDS developed less frequently among patients aged>or=85 years. The incidence of and risk factors for ARDS among elderly patients with community-acquired pneumonia (CAP) have not been well characterized. The clinical details of 221 consecutive patients aged>or=65 years, who were admitted with CAP during the period April 2006 to June 2008, were investigated by review of patient charts. Clinical variables and laboratory data at admission for CAP were compared between patients with and without ARDS. Eighteen patients (8.1%) developed ARDS 1-5 days after admission. The mortality rate was 44% in patients with ARDS and 10.3% in those without ARDS (P<0.001). The incidence of ARDS was 8.5-20% among patients aged<85 years and 1.1% in patients aged>or=85 years (P<0.001), while overall mortality rates were not significantly different among the age groups. Predictors for the development of ARDS included higher serum levels of CRP and glucose, lower PaO2/fraction of inspired O2 (FiO2), PaCO2 and HCO3-, and the presence of systemic inflammatory response syndrome at admission. ARDS developed less frequently among patients with pneumonia associated with oropharyngeal aspiration (AP). Multivariate analysis indicated that lower age, serum glucose, pre-existence of systemic inflammatory response syndrome and non-oropharyngeal AP were significant risk factors for ARDS. The Pneumonia Severity Index and confusion, urea, respiratory rate, blood pressure, age>or=65 score were not correlated with the incidence of ARDS. Predictors for ARDS appeared to differ from the determinants of severity of CAP in the elderly. ARDS developed less frequently in patients aged>or=85 years and in those with oropharyngeal AP. It is important to identify subjects at high risk for ARDS upon admission and to observe them closely.

Risk Factors for ARDS in Patients Receiving Mechanical Ventilation for &gt; 48h

Risk Factors for ARDS in Patients Receiving Mechanical Ventilation for &gt; 48h

Animal models of acute lung injury

Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.

Risk Factors for ARDS in Patients Receiving Mechanical Ventilation for > 48 h

Low tidal volume (Vt) ventilation for ARDS is a well-accepted concept. However, controversy persists regarding the optimal ventilator settings for patients without ARDS receiving mechanical ventilation. This study tested the hypothesis that ventilator settings influence the development of new ARDS. Retrospective analysis of patients from the Multi Parameter Intelligent Monitoring of Intensive Care-II project database who received mechanical ventilation for > or = 48 h between 2001 and 2005. A total of 2,583 patients required > 48 h of ventilation. Of 789 patients who did not have ARDS at hospital admission, ARDS developed in 152 patients (19%). Univariate analysis revealed high peak inspiratory pressure (odds ratio [OR], 1.53 per SD; 95% confidence interval [CI], 1.28 to 1.84), increasing positive end-expiratory pressure (OR, 1.35 per SD; 95% CI, 1.15 to 1.58), and Vt (OR, 1.36 per SD; 95% CI, 1.12 to 1.64) to be significant risk factors. Major nonventilator risk factors for ARDS included sepsis, low pH, elevated lactate, low albumin, transfusion of packed RBCs, transfusion of plasma, high net fluid balance, and low respiratory compliance. Multivariable logistic regression showed that peak pressure (OR, 1.31 per SD; 95% CI, 1.08 to 1.59), high net fluid balance (OR, 1.3 per SD; 95% CI, 1.09 to 1.56), transfusion of plasma (OR, 1.26 per SD; 95% CI, 1.07 to 1.49), sepsis (OR, 1.57; 95% CI, 1.00 to 2.45), and Vt (OR, 1.29 per SD; 95% CI, 1.02 to 1.52) were significantly associated with the development of ARDS. The associations between the development of ARDS and clinical interventions, including high airway pressures, high Vt, positive fluid balance, and transfusion of blood products, suggests that ARDS may be a preventable complication in some cases.

Polymorphism in the Surfactant Protein-B Gene, Gender, and the Risk of Direct Pulmonary Injury and ARDS

Major risk factors for ARDS have been identified. However, only a minority of patients with such risks develops ARDS. It is likely that, given the same type and degree of insult, there are heritable determinants of susceptibility to ARDS. To investigate the possibility of variable genetic susceptibility to ARDS, we examined the association between ARDS and a polymorphism in intron 4 of the surfactant protein-B (SP-B) gene. Nested case-control study conducted from September 1999 to March 2001. Four adult medical and surgical ICUs at a tertiary academic center. One hundred eighty-nine patients meeting study criteria for a defined risk factor for ARDS were enrolled and prospectively followed. Seventy-two patients (38%) developed ARDS. After stratification by gender and adjustment for potential confounders, there was a significantly increased odds for women with the variant SP-B gene to develop ARDS compared to women homozygous for the wild-type allele (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.1 to 18.8; p = 0.03). Women with the variant SP-B polymorphism also had significantly increased odds of having a direct pulmonary injury such as aspiration or pneumonia as a risk factor for ARDS as opposed to an indirect pulmonary risk for ARDS (OR, 4.6; 95% CI, 1.1 to 19.9; p = 0.04). No such association with ARDS or direct pulmonary injury was found for men. The variant polymorphism of the SP-B gene is associated with ARDS and with direct pulmonary injury in women, but not in men. Further study is needed to confirm the association between the variant SP-B gene, and gender, ARDS, and direct pulmonary injury.