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Background: Cardiogenic shock due to acute myocardial infarction (AMI-CS) is associated with significant short- and long-term morbidity and mortality. Despite this, little is known about associated cost. Objectives: The purpose of this study was to evaluate the health care costs and resource use associated with AMI-CS using administrative data from the province of Ontario, Canada. Methods: This was a retrospective cohort study of adult patients with AMI-CS from April 2009 to March 2019. One-year costs following index admission were reported at an individual level. We used generalized linear models to identify factors associated with increased cost. We stratified patients by revascularization strategy to compare cost in each group and examined total cost at a patient level per individual fiscal year. Results: We included 9,789 consecutive patients with AMI-CS across 135 centers in Ontario (mean age 70.5 years; 67.7% male). Mortality in-hospital was 30.2%, and mortality at 2 years was 45.9%. The median inpatient cost per patient was $23,912 (IQR: $12,234-$41,833) with a median total 1-year cost of $37,913 (IQR: $20,113-$66,582). The median 1-year cost was $17,730 (IQR: $9,323-$38,379) for those who died in hospital, and $45,713 (IQR: $29,688-$77,683) for those surviving to discharge, with $12,719 (IQR: $4,262-$35,275) occurring after discharge. Patients who received coronary artery bypass grafting incurred the highest cost among revascularization groups. No significant differences were observed in cost per fiscal year from 2009 to 2019. Conclusions: AMI-CS is associated with significant health care costs, both during the index hospitalization and following discharge. To optimize cost-effectiveness, future therapies should aim to reduce disability in addition to improving mortality.
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Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots (DBSs) to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels. Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than 6 months earlier, spike levels fell notably and continuously for the 9-month post-vaccination. In contrast, among adults infected within 6 months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than 6 months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% confidence interval 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the coronavirus disease 2019 (COVID-19) weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity. Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected DBSs are a practicable biological surveillance platform. Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
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Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Vacinação , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Canadá/epidemiologia , SARS-CoV-2/imunologia , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Estudos de Coortes , Idoso , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto JovemRESUMO
Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation. Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin. Methods: Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21. Results: Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low. Conclusions: Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis.
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PURPOSE: Cardiogenic shock secondary to acute myocardial infarction (AMI-CS) is associated with substantial short- and long-term morbidity and mortality. However, there are limited data on mental health sequelae that survivors experience following discharge. METHODS: We conducted a retrospective, population-based cohort study in Ontario, Canada of critically ill adult (≥ 18 years) survivors of AMI-CS, admitted to hospital between April 1, 2009 and March 31, 2019. We compared these patients to AMI survivors without shock. We captured outcome data using linked health administrative databases. The primary outcome was a new mental health diagnosis (a composite of mood, anxiety, or related disorders; schizophrenia/psychotic disorders; and other mental health disorders) following hospital discharge. We secondarily evaluated incidence of deliberate self-harm and death by suicide. We compared patients using overlap propensity score-weighted, cause-specific proportional hazard models. RESULTS: We included 7812 consecutive survivors of AMI-CS, from 135 centers. Mean age was 68.4 (standard deviation (SD) 12.2) years, and 70.3% were male. Median follow-up time was 767 days (interquartile range (IQR) 225-1682). Incidence of new mental health diagnosis among AMI-CS survivors was 109.6 per 1,000 person-years (95% confidence interval (CI) 105.4-113.9), compared with 103.8 per 1000 person-years (95% CI 102.5-105.2) among AMI survivors without shock. After propensity score adjustment, there was no difference in the risk of new mental health diagnoses following discharge [hazard ratio (HR) 0.99 (95% CI 0.94-1.03)]. Factors associated with new mental health diagnoses following AMI-CS included female sex, pre-existing mental health diagnoses, and discharge to a long-term hospital or rehabilitation institute. CONCLUSION: Survivors of AMI-CS experience substantial mental health morbidity following discharge. Risk of new mental health diagnoses was comparable between survivors of AMI with and without shock. Future research on interventions to mitigate psychiatric sequelae after AMI-CS is warranted.
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Infarto do Miocárdio , Choque Cardiogênico , Sobreviventes , Humanos , Masculino , Feminino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/psicologia , Infarto do Miocárdio/epidemiologia , Choque Cardiogênico/psicologia , Choque Cardiogênico/etiologia , Choque Cardiogênico/epidemiologia , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Ontário/epidemiologia , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Transtornos Mentais/complicações , Estudos de Coortes , Idoso de 80 Anos ou mais , Incidência , Saúde MentalRESUMO
INTRODUCTION: Acute respiratory distress syndrome (ARDS), marked by acute hypoxemia and bilateral pulmonary infiltrates, has been defined in multiple ways since its first description. This Delphi study aims to collect global opinions on the conceptual framework of ARDS, assess the usefulness of components within current and past definitions and investigate the role of subphenotyping. The varied expertise of the panel will provide valuable insights for refining future ARDS definitions and improving clinical management. METHODS: A diverse panel of 35-40 experts will be selected based on predefined criteria. Multiple choice questions (MCQs) or 7-point Likert-scale statements will be used in the iterative Delphi rounds to achieve consensus on key aspects related to the utility of definitions and subphenotyping. The Delphi rounds will be continued until a stable agreement or disagreement is achieved for all statements. ANALYSIS: Consensus will be considered as reached when a choice in MCQs or Likert-scale statement achieved ≥80% of votes for agreement or disagreement. The stability will be checked by non-parametric χ2 tests or Kruskal Wallis test starting from the second round of Delphi process. A p-value ≥0.05 will be used to define stability. ETHICS AND DISSEMINATION: The study will be conducted in full concordance with the principles of the Declaration of Helsinki and will be reported according to CREDES guidance. This study has been granted an ethical approval waiver by the NMC Healthcare Regional Research Ethics Committee, Dubai (NMCHC/CR/DXB/REC/APP/002), owing to the nature of the research. Informed consent will be obtained from all panellists before the start of the Delphi process. The study will be published in a peer-review journal with the authorship agreed as per ICMJE requirements. TRIAL REGISTRATION NUMBER: NCT06159465.
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Consenso , Técnica Delphi , Síndrome do Desconforto Respiratório , Humanos , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/terapia , Projetos de PesquisaRESUMO
BACKGROUND: Pre-clinical studies suggest that dyssynchronous diaphragm contractions during mechanical ventilation may cause acute diaphragm dysfunction. We aimed to describe the variability in diaphragm contractile loading conditions during mechanical ventilation and to establish whether dyssynchronous diaphragm contractions are associated with the development of impaired diaphragm dysfunction. METHODS: In patients receiving invasive mechanical ventilation for pneumonia, septic shock, acute respiratory distress syndrome, or acute brain injury, airway flow and pressure and diaphragm electrical activity (Edi) were recorded hourly around the clock for up to 7 days. Dyssynchronous post-inspiratory diaphragm loading was defined based on the duration of neural inspiration after expiratory cycling of the ventilator. Diaphragm function was assessed on a daily basis by neuromuscular coupling (NMC, the ratio of transdiaphragmatic pressure to diaphragm electrical activity). RESULTS: A total of 4508 hourly recordings were collected in 45 patients. Edi was low or absent (≤ 5 µV) in 51% of study hours (median 71 h per patient, interquartile range 39-101 h). Dyssynchronous post-inspiratory loading was present in 13% of study hours (median 7 h per patient, interquartile range 2-22 h). The probability of dyssynchronous post-inspiratory loading was increased with reverse triggering (odds ratio 15, 95% CI 8-35) and premature cycling (odds ratio 8, 95% CI 6-10). The duration and magnitude of dyssynchronous post-inspiratory loading were associated with a progressive decline in diaphragm NMC (p < 0.01 for interaction with time). CONCLUSIONS: Dyssynchronous diaphragm contractions may impair diaphragm function during mechanical ventilation. TRIAL REGISTRATION: MYOTRAUMA, ClinicalTrials.gov NCT03108118. Registered 04 April 2017 (retrospectively registered).
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Respiração Artificial , Síndrome do Desconforto Respiratório , Humanos , Diafragma , Respiração Artificial/efeitos adversos , Tórax , Ventiladores MecânicosRESUMO
BACKGROUND: The bag-valve-mask (BVM) or manual resuscitator bag is used as a first-line technique to ventilate patients with respiratory failure. Volume-restricted manual resuscitator bags (eg, pediatric bags) have been suggested to minimize overventilation and associated complications. There are studies that both support and caution against the use of a pediatric resuscitator bag to ventilate an adult patient. In this study, we evaluated the ability of pre-hospital clinicians to adequately ventilate an adult manikin with both an adult- and pediatric-size manual resuscitator bag without the assistance of an advanced airway or airway adjunct device. METHODS: This study was conducted at an international conference in 2022. Conference attendees with pre-hospital health care experience were recruited to ventilate an adult manikin using a BVM for 1 min with both an adult and pediatric resuscitator bag, without the use of adjunct airway devices, while 6 ventilatory variables were collected or calculated: tidal volume (VT), breathing frequency, adequate breaths (VT > 150 mL), proportion of adequate breaths, peak inspiratory pressure (PIP), and estimated alveolar ventilation (EAV). RESULTS: A total of 208 participants completed the study. Ventilation with the adult-sized BVM delivered an average VT of 290.4 mL compared to 197.1 mL (P < .001) when using the pediatric BVM. PIP with the adult BVM was higher than with the pediatric BVM (10.6 cm H2O vs 8.6 cm H2O, P < .001). The median EAV with the adult bag (1,138.1 [interquartile range [IQR] 194.0-2,869.9] mL/min) was markedly greater than with the pediatric BVM (67.7 [IQR 0-467.3] mL/min, P < .001). CONCLUSIONS: Both pediatric- and adult-sized BVM provided lower ventilation volumes than those recommended by professional guidelines for an adult. Ventilation with the pediatric BVM was significantly worse than with the adult bag when ventilating a simulated adult subject.
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Manequins , Respiração Artificial , Volume de Ventilação Pulmonar , Humanos , Adulto , Respiração Artificial/instrumentação , Respiração Artificial/métodos , Insuficiência Respiratória/terapia , Masculino , Feminino , Desenho de Equipamento , Taxa RespiratóriaRESUMO
PURPOSE: Assessing efficacy of electrical impedance tomography (EIT) in optimizing positive end-expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) patients to enhance respiratory system mechanics and prevent ventilator-induced lung injury (VILI), compared to traditional methods. METHODS: We carried out a systematic review and meta-analysis, spanning literature from January 2012 to May 2023, sourced from Scopus, PubMed, MEDLINE (Ovid), Cochrane, and LILACS, evaluated EIT-guided PEEP strategies in ARDS versus conventional methods. Thirteen studies (3 randomized, 10 non-randomized) involving 623 ARDS patients were analyzed using random-effects models for primary outcomes (respiratory mechanics and mechanical power) and secondary outcomes (PaO2/FiO2 ratio, mortality, stays in intensive care unit (ICU), ventilator-free days). RESULTS: EIT-guided PEEP significantly improved lung compliance (n = 941 cases, mean difference (MD) = 4.33, 95% confidence interval (CI) [2.94, 5.71]), reduced mechanical power (n = 148, MD = - 1.99, 95% CI [- 3.51, - 0.47]), and lowered driving pressure (n = 903, MD = - 1.20, 95% CI [- 2.33, - 0.07]) compared to traditional methods. Sensitivity analysis showed consistent positive effect of EIT-guided PEEP on lung compliance in randomized clinical trials vs. non-randomized studies pooled (MD) = 2.43 (95% CI - 0.39 to 5.26), indicating a trend towards improvement. A reduction in mortality rate (259 patients, relative risk (RR) = 0.64, 95% CI [0.45, 0.91]) was associated with modest improvements in compliance and driving pressure in three studies. CONCLUSIONS: EIT facilitates real-time, individualized PEEP adjustments, improving respiratory system mechanics. Integration of EIT as a guiding tool in mechanical ventilation holds potential benefits in preventing ventilator-induced lung injury. Larger-scale studies are essential to validate and optimize EIT's clinical utility in ARDS management.
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Impedância Elétrica , Respiração com Pressão Positiva , Síndrome do Desconforto Respiratório , Tomografia , Lesão Pulmonar Induzida por Ventilação Mecânica , Humanos , Respiração com Pressão Positiva/métodos , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/fisiopatologia , Tomografia/métodos , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Mecânica Respiratória/fisiologiaRESUMO
Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.
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Síndrome do Desconforto Respiratório , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/terapia , Oximetria , OxigênioRESUMO
BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and clinical trials are conflicting and the factors influencing outcome have not been well established. METHODS: We conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach. FINDINGS: We included 29 observational and randomized studies involving 7,397 patients. Factors with moderate or high certainty of association with increased survival with favourable functional outcome include pre-arrest patient factors, such as younger age (odds ratio (OR) 2.13, 95% CI 1.52 to 2.99) and female sex (OR 1.37, 95% CI 1.11 to 1.70), as well as intra-arrest factors, such as shockable rhythm (OR 2.79, 95% CI 2.04 to 3.80), witnessed arrest (OR 1.68 (95% CI 1.16 to 2.42), bystander CPR (OR 1.55, 95% CI 1.19 to 2.01), return of spontaneous circulation (OR 2.81, 95% CI 2.19 to 3.61) and shorter time to cannulation (OR 1.14, 95% CI 1.17 to 1.69 per 10 minutes). INTERPRETATION: The findings of this review confirm several clinical concepts wellestablished in the cardiac arrest literature and their applicability to the patient for whom ECPR is considered - that is, the impact of pre-existing patient factors, the benefit of timely and effective CPR, as well as the prognostic importance of minimizing low-flow time. We advocate for the thoughtful consideration of these prognostic factors as part of a risk stratification framework when evaluating a patient's potential candidacy for ECPR.
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Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Feminino , Parada Cardíaca Extra-Hospitalar/terapia , Prognóstico , Razão de Chances , Estudos RetrospectivosRESUMO
Despite similar infection rates, COVID-19 has resulted in more deaths in men than women. To understand the underlying mechanisms behind this sex-biased difference in disease severity, we infected K18-human angiotensin converting enzyme 2 (ACE2) mice of both sexes with SARS-CoV-2. Our study revealed a unique protein expression profile in the lung microenvironment of female mice. As a result, they were less vulnerable to severe infection, with higher ACE2 expression and a higher estrogen receptor α (ERα)/androgen receptor (AR) ratio that led to increased antiviral factor levels. In male mice, inhaling recombinant ACE2 neutralized the virus and maintained the ERα/AR ratio, thereby protecting the lungs. Our findings suggest that inhaling recombinant ACE2 could serve as a decoy receptor against SARS-CoV-2 and protect male mice by offsetting ERα-associated protective mechanisms. Additionally, our study supports the potential effectiveness of recombinant ACE2 therapy in human lung organoids infected with the Delta variant.
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OBJECTIVES: To assess the value of machine learning approaches in the development of a multivariable model for early prediction of ICU death in patients with acute respiratory distress syndrome (ARDS). DESIGN: A development, testing, and external validation study using clinical data from four prospective, multicenter, observational cohorts. SETTING: A network of multidisciplinary ICUs. PATIENTS: A total of 1,303 patients with moderate-to-severe ARDS managed with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed and tested prediction models in 1,000 ARDS patients. We performed logistic regression analysis following variable selection by a genetic algorithm, random forest and extreme gradient boosting machine learning techniques. Potential predictors included demographics, comorbidities, ventilatory and oxygenation descriptors, and extrapulmonary organ failures. Risk modeling identified some major prognostic factors for ICU mortality, including age, cancer, immunosuppression, Pa o2 /F io2 , inspiratory plateau pressure, and number of extrapulmonary organ failures. Together, these characteristics contained most of the prognostic information in the first 24 hours to predict ICU mortality. Performance with machine learning methods was similar to logistic regression (area under the receiver operating characteristic curve [AUC], 0.87; 95% CI, 0.82-0.91). External validation in an independent cohort of 303 ARDS patients confirmed that the performance of the model was similar to a logistic regression model (AUC, 0.91; 95% CI, 0.87-0.94). CONCLUSIONS: Both machine learning and traditional methods lead to promising models to predict ICU death in moderate/severe ARDS patients. More research is needed to identify markers for severity beyond clinical determinants, such as demographics, comorbidities, lung mechanics, oxygenation, and extrapulmonary organ failure to guide patient management.
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Síndrome do Desconforto Respiratório , Humanos , Unidades de Terapia Intensiva , Pulmão , Estudos Prospectivos , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapiaRESUMO
In acute lung injury, the lung endothelial barrier is compromised. Loss of endothelial barrier integrity occurs in association with decreased levels of the tight junction protein claudin-5. Restoration of their levels by gene transfection may improve the vascular barrier, but how to limit transfection solely to regions of the lung that are injured is unknown. We hypothesized that thoracic ultrasound in combination with intravenous microbubbles (USMBs) could be used to achieve regional gene transfection in injured lung regions and improve endothelial barrier function. Since air blocks ultrasound energy, insonation of the lung is only achieved in areas of lung injury (edema and atelectasis); healthy lung is spared. Cavitation of the microbubbles achieves local tissue transfection. Here we demonstrate successful USMB-mediated gene transfection in the injured lungs of mice. After thoracic insonation, transfection was confined to the lung and only occurred in the setting of injured (but not healthy) lung. In a mouse model of acute lung injury, we observed downregulation of endogenous claudin-5 and an acute improvement in lung vascular leakage and in oxygenation after claudin-5 overexpression by transfection. The improvement occurred without any impairment of the immune response as measured by pathogen clearance, alveolar cytokines, and lung histology. In conclusion, USMB-mediated transfection targets injured lung regions and is a novel approach to the treatment of lung injury.NEW & NOTEWORTHY Acute respiratory distress syndrome is characterized by spatial heterogeneity, with severely injured lung regions adjacent to relatively normal areas. This makes targeting treatment to the injured regions difficult. Here we use thoracic ultrasound and intravenous microbubbles (USMBs) to direct gene transfection specifically to injured lung regions. Transfection of the tight junction protein claudin-5 improved oxygenation and decreased vascular leakage without impairing innate immunity. These findings suggest that USMB is a novel treatment for ARDS.