Heterogeneity Of Acute Respiratory Distress Syndrome Research Articles

Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup.

Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury characterized by the damage of alveolar epithelial cells and pulmonary capillary endothelial cells. It is mainly manifested by non-cardiogenic pulmonary edema, resulting from intrapulmonary and extrapulmonary risk factors. ARDS is often accompanied by immune system disturbance, both locally in the lungs and systemically. As a common heterogeneous disease in critical care medicine, researchers are often faced with the failure of clinical trials. Latent class analysis had been used to compensate for poor outcomes and found that targeted treatment after subgrouping contribute to ARDS therapy. The subphenotype of ARDS caused by sepsis has garnered attention due to its refractory nature and detrimental consequences. Sepsis stands as the most predominant extrapulmonary cause of ARDS, accounting for approximately 32% of ARDS cases. Studies indicate that sepsis-induced ARDS tends to be more severe than ARDS caused by other factors, leading to poorer prognosis and higher mortality rate. This comprehensive review delves into the immunological mechanisms of sepsis-ARDS, the heterogeneity of ARDS and existing research on targeted treatments, aiming to providing mechanism understanding and exploring ideas for accurate treatment of ARDS or sepsis-ARDS.

Endothelial dysfunction triggers acute respiratory distress syndrome in patients with sepsis: a narrative review.

Acute respiratory distress syndrome (ARDS) is a severe organ failure occurring mainly in critically ill patients as a result of different types of insults such as sepsis, trauma or aspiration. Sepsis is the main cause of ARDS, and it contributes to a high mortality and resources consumption both in hospital setting and in the community. ARDS develops mainly an acute respiratory failure with severe and often refractory hypoxemia. ARDS also has long term implications and sequelae. Endothelial damage plays an important role in the pathogenesis of ARDS. Understanding the mechanisms of ARDS presents opportunities for novel diagnostic and therapeutic targets. Biochemical signals can be used in concert to identify and classify patients into ARDS phenotypes allowing earlier effective treatment with personalised therapies. This is a narrative review where we aimed to flesh out the pathogenetic mechanisms and heterogeneity of ARDS. We examine the links between endothelium damage and its contribution to organ failure. We have also investigated future strategies for treatment with a special emphasis in endothelial damage.

Insights into COVID-19-associated critical illness: a narrative review.

Since the outbreak of the 2019 novel coronavirus disease (COVID-19), acute respiratory distress syndrome (ARDS) and sepsis resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have surged in intensive care units around the world. The heterogeneity of ARDS and sepsis has long been observed, and multiple subphenotypes and endotypes correlated with different outcomes and treatment response have been identified in the search for treatable traits. Despite their similarity to typical ARDS and sepsis, COVID-19-associated ARDS and sepsis harbor distinct features, raising the question as to whether they could be considered as subphenotypes or endotypes of the historical syndromes and, accordingly, benefit from specific therapeutic strategies. This review aimed to summarize and discuss the current knowledge of COVID-19-associated critical illness and the intrinsic subphenotypes or endotypes. Literature on the pathogenesis of COVID-19 and the subphenotyping of COVID-19-associated critical illness was derived from the PubMed database and reviewed. Accumulating evidence, varying from clinical observation to basic research, has contributed to revealing the fundamental pathophysiological features of severe COVID-19 and has advanced our knowledge of the disease. COVID-19-associated ARDS and sepsis exhibit some distinctive features compared to the classic syndromes, including remarkable vascular abnormality and coagulopathy, and distinct respiratory mechanics and immune response. Some conventional subphenotypes derived from classic ARDS and sepsis have been validated in COVID-19, while novel subphenotypes and endotypes have also been identified in patients with this disease, who experience variable clinical outcomes and treatment responses. Subphenotyping of COVID-19-associated ARDS and sepsis can provide new insights into the development and management of these illnesses.

The role of the alveolar epithelial glycocalyx in acute respiratory distress syndrome.

The alveolar epithelial glycocalyx is a dense anionic layer of glycosaminoglycans (GAGs) and proteoglycans that lines the apical surface of the alveolar epithelium. In contrast to the pulmonary endothelial glycocalyx, which has well-established roles in vascular homeostasis and septic organ dysfunction, the alveolar epithelial glycocalyx is less understood. Recent preclinical studies demonstrated that the epithelial glycocalyx is degraded in multiple murine models of acute respiratory distress syndrome (ARDS), particularly those that result from inhaled insults (so-called "direct" lung injury), leading to shedding of GAGs into the alveolar airspaces. Epithelial glycocalyx degradation also occurs in humans with respiratory failure, as quantified by analysis of airspace fluid obtained from ventilator heat moisture exchange (HME) filters. In patients with ARDS, GAG shedding correlates with the severity of hypoxemia and is predictive of the duration of respiratory failure. These effects may be mediated by surfactant dysfunction, as targeted degradation of the epithelial glycocalyx in mice was sufficient to cause increased alveolar surface tension, diffuse microatelectasis, and impaired lung compliance. In this review, we describe the structure of the alveolar epithelial glycocalyx and the mechanisms underlying its degradation during ARDS. We additionally review the current state of knowledge regarding the attributable effect of epithelial glycocalyx degradation in lung injury pathogenesis. Finally, we address glycocalyx degradation as a potential mediator of ARDS heterogeneity, and the subsequent value of point-of-care quantification of GAG shedding to potentially identify patients who are most likely to respond to pharmacological agents aimed at attenuating glycocalyx degradation.

Advancing Precision Medicine for the Diagnosis and Treatment of Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a common and life-threatening cause of respiratory failure. Despite decades of research, there are no effective pharmacologic therapies to treat this disease process and mortality remains high. The shortcomings of prior translational research efforts have been increasingly attributed to the heterogeneity of this complex syndrome, which has led to an increased focus on elucidating the mechanisms underlying the interpersonal heterogeneity of ARDS. This shift in focus aims to move the field towards personalized medicine by defining subgroups of ARDS patients with distinct biology, termed endotypes, to quickly identify patients that are most likely to benefit from mechanism targeted treatments. In this review, we first provide a historical perspective and review the key clinical trials that have advanced ARDS treatment. We then review the key challenges that exist with regards to the identification of treatable traits and the implementation of personalized medicine approaches in ARDS. Lastly, we discuss potential strategies and recommendations for future research that we believe will aid in both understanding the molecular pathogenesis of ARDS and the development of personalized treatment approaches.

Research Progress on Phenotypic Classification of Acute Respiratory Distress Syndrome: A Narrative Review.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome that is characterized by an acute onset and refractory hypoxemia. It remains an important contributor to high mortality in critically ill patients, and the majority of clinical randomized controlled trials on ARDS provide underwhelming findings, which is attributed in large part to its pathophysiological and clinical heterogeneity, among other aspects. It is now widely accepted that ARDS is highly heterogeneous, growing evidences support this. ARDS phenotypic and subphenotypic studies aim to further differentiate and identify ARDS heterogeneity in the hope that clinicians can benefit from it, then can diagnose ARDS faster and more accurately and provide targeted treatments. This review collates and evaluates the major phenotype-related research advances of recent years, with a specific focus on ARDS biomarkers and clinical factors.

New Insights into Clinical and Mechanistic Heterogeneity of the Acute Respiratory Distress Syndrome: Summary of the Aspen Lung Conference 2021.

Clinical and molecular heterogeneity are common features of human disease. Understanding the basis for heterogeneity has led to major advances in therapy for many cancers and pulmonary diseases such as cystic fibrosis and asthma. Although heterogeneity of risk factors, disease severity, and outcomes in survivors are common features of the acute respiratory distress syndrome (ARDS), many challenges exist in understanding the clinical and molecular basis for disease heterogeneity and using heterogeneity to tailor therapy for individual patients. This report summarizes the proceedings of the 2021 Aspen Lung Conference, which was organized to review key issues related to understanding clinical and molecular heterogeneity in ARDS. The goals were to review new information about ARDS phenotypes, to explore multicellular and multisystem mechanisms responsible for heterogeneity, and to review how best to account for clinical and molecular heterogeneity in clinical trial design and assessment of outcomes. The report concludes with recommendations for future research to understand the clinical and basic mechanisms underlying heterogeneity in ARDS to advance the development of new treatments for this life-threatening critical illness.

Early prediction of moderate-to-severe condition of inhalation-induced acute respiratory distress syndrome via interpretable machine learning

BackgroundSeveral studies have investigated the correlation between physiological parameters and the risk of acute respiratory distress syndrome (ARDS), in addition, etiology-associated heterogeneity in ARDS has become an emerging topic quite recently; however, the intersection between the two, which is early prediction of target conditions in etiology-specific ARDS, has not been well-studied. We aimed to develop and validate a machine-learning model for the early prediction of moderate-to-severe condition of inhalation-induced ARDS.MethodsClinical expertise was applied with data-driven analysis. Using data from electronic intensive care units (retrospective derivation cohort) and the three most accessible vital signs (i.e. heart rate, temperature, and respiratory rate) together with feature engineering, we applied a random forest approach during the time window of 90 h that ended 6 h prior to the onset of moderate-to-severe respiratory failure (the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤ 200 mmHg).ResultsThe trained random forest classifier was validated using two independent validation cohorts, with an area under the curve of 0.9127 (95% confidence interval 0.8713–0.9542) and 0.9026 (95% confidence interval 0.8075–1), respectively. A Stable and Interpretable RUle Set (SIRUS) was used to extract rules from the RF to provide guidelines for clinicians. We identified several predictive factors, including resp_96h_6h_min < 9, resp_96h_6h_mean ≥ 16.1, HR_96h_6h_mean ≥ 102, and temp_96h_6h_max > 100, that could be used for predicting inhalation-induced ARDS (moderate-to-severe condition) 6 h prior to onset in critical care units. (‘xxx_96h_6h_min/mean/max’: the minimum/mean/maximum values of the xxx vital sign collected during a 90 h time window beginning 96 h prior to the onset of ARDS and ending 6 h prior to the onset from every recorded blood gas test).ConclusionsThis newly established random forest‑based interpretable model shows good predictive ability for moderate-to-severe inhalation-induced ARDS and may assist clinicians in decision-making, as well as facilitate the enrolment of patients in prevention programmes to improve their outcomes.

Research progress on metabolomics of acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a clinically and biologically heterogeneous disease. Given the heterogeneity of ARDS due to the wide range of etiological, clinical, and molecular manifestations, the current scientific consensus is that ARDS is not a single disease, but rather a set of diseases that require further research to properly classify and identify. Metabonomics, as a rapidly developing field of systems biology, has made many breakthroughs in science and medicine as an interdisciplinary platform. Metabonomics provides an important opportunity for the discovery and analysis of biomarkers in the diagnosis of ARDS, which is expected to reveal the biological process behind ARDS and show great potential in solving the heterogeneity and severity assessment of ARDS. This review focuses on the literature of ARDS metabonomics and summarizes the progress of ARDS metabonomics research and the main obstacles.

Cigarette Smoke Exposure and Acute Respiratory Distress Syndrome in Sepsis: Epidemiology, Clinical Features, and Biologic Markers.

Rationale: Cigarette smoke exposure is associated with an increased risk of developing acute respiratory distress syndrome (ARDS) in trauma, transfusion, and nonpulmonary sepsis. It is unknown whether this relationship exists in the general sepsis population. Furthermore, it is unknown if patients with ARDS have differences in underlying biology based on smoking status. Objectives: To assess the relationship between cigarette smoke exposure and ARDS in sepsis and identify tobacco-related biomarkers of lung injury. Methods: We studied a prospective cohort of 592 patients with sepsis from 2009 to 2017. Plasma cotinine and urine NNAL [urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol] were measured to categorize smoking status. Plasma biomarkers of inflammation and lung injury were measured, including in a smaller cohort of trauma patients with ARDS to increase generalizability. Measurements and Main Results: Passive and active smoking were associated with increased odds of developing ARDS in patients with sepsis. Among patients with sepsis and ARDS, active cigarette smokers were younger and had lower severity of illness than nonsmokers. Patients with ARDS with cigarette smoke exposure had lower plasma levels of IL-8 (P = 0.01) and sTNFR-1 (soluble tumor necrosis factor 1; P = 0.01) compared with those without exposure. Similar biomarker patterns were observed in blunt trauma patients with ARDS. Conclusions: Passive and active smoking are associated with an increased risk of developing ARDS in patients with pulmonary and nonpulmonary sepsis. Among patients with ARDS, those with cigarette smoke exposure have less systemic inflammation, while active smokers also have lower severity of illness compared with nonsmokers, suggesting that smoking contributes to biological heterogeneity in ARDS.

Etiology-associated heterogeneity in acute respiratory distress syndrome: a retrospective cohort study

BackgroundHeterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described.MethodsIn this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal–Wallis rank tests and Chi-squared tests were used to compare between-etiology differences.ResultsFrom 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia.ConclusionThis study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.

ABO blood type: a window into the genetics of acute respiratory distress syndrome susceptibility.

The genetic factors that determine a patient's risk for developing the acute respiratory distress syndrome (ARDS) remain understudied. In this issue of the JCI, Reilly and colleagues analyzed data from three cohorts of critically ill patients and observed an association between the ABO allele A1 and the onset of moderate-severe ARDS. This association was most notable in patients with non-pulmonary sepsis (an indirect, vasculature-targeted mechanism of lung injury) and persisted in patients who lacked epithelial expression of the A antigen, suggesting an endothelial mechanism of A1-associated ARDS susceptibility. Critically ill patients with blood type A had increased circulating concentrations of endothelium-derived glycoproteins such as von Willebrand factor and soluble thrombomodulin, and marginal lungs from blood type A donors were less likely to recover function during ex vivo perfusion. These findings implicate A antigen glycosylation of endothelial cells as a critical, genetically determined risk factor for indirect lung injury that may contribute to the mechanistic heterogeneity of ARDS.

Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Guideline-Driven Care Should Be Our Natural Reflex.

Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Guideline-Driven Care Should Be Our Natural Reflex.

Systems Biology ARDS Research with a Focus on Metabolomics.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome that inflicts a considerably heavy toll in terms of morbidity and mortality. While there are multitudes of conditions that can lead to ARDS, the vast majority of ARDS cases are caused by a relatively small number of diseases, especially sepsis and pneumonia. Currently, there is no clinically agreed upon reliable diagnostic test for ARDS, and the detection or diagnosis of ARDS is based on a constellation of laboratory and radiological tests in the absence of evidence of left ventricular dysfunction, as specified by the Berlin definition of ARDS. Virtually all the ARDS biomarkers to date have been proven to be of very limited clinical utility. Given the heterogeneity of ARDS due to the wide variation in etiology, clinical and molecular manifestations, there is a current scientific consensus agreement that ARDS is not just a single entity but rather a spectrum of conditions that need further study for proper classification, the identification of reliable biomarkers and the adequate institution of therapeutic targets. This scoping review aims to elucidate ARDS omics research, focusing on metabolomics and how metabolomics can boost the study of ARDS biomarkers and help to facilitate the identification of ARDS subpopulations.

An NMR based panorama of the heterogeneous biology of acute respiratory distress syndrome (ARDS) from the standpoint of metabolic biomarkers.

Acute respiratory distress syndrome (ARDS), manifested by intricate etiology and pathophysiology, demands careful clinical surveillance due to its high mortality and imminent life support measures. NMR based metabolomics provides an approach for ARDS which culminates from a wide spectrum of illness thereby confounding early manifestation and prognosis predictors. 1 H NMR with its manifold applications in critical disease settings can unravel the biomarker of ARDS thus holding potent implications by providing surrogate endpoints of clinical utility. NMR metabolomics which is the current apogee platform of omics trilogy is contributing towards the possible panacea of ARDS by subsequent validation of biomarker credential on larger datasets. In the present review, the physiological derangements that jeopardize the whole metabolic functioning in ARDS are exploited and the biomarkers involved in progression are addressed and substantiated. The following sections of the review also outline the clinical spectrum of ARDS from the standpoint of NMR based metabolomics which is an emerging element of systems biology. ARDS is the main premise of intensivists textbook, which has been thoroughly reviewed along with its incidence, progressive stages of severity, new proposed diagnostic definition, and the preventive measures and the current pitfalls of clinical management. The advent of new therapies, the need for biomarkers, the methodology and the contemporary promising approaches needed to improve survival and address heterogeneity have also been evaluated. The review has been stepwise illustrated with potent biometrics employed to selectively pool out differential metabolites as diagnostic markers and outcome predictors. The following sections have been drafted with an objective to better understand ARDS mechanisms with predictive and precise biomarkers detected so far on the basis of underlying physiological parameters having close proximity to diseased phenotype. The aim of this review is to stimulate interest in conducting more studies to help resolve the complex heterogeneity of ARDS with biomarkers of clinical utility and relevance.

Distinct Metabolic Endotype Mirroring Acute Respiratory Distress Syndrome (ARDS) Subphenotype and its Heterogeneous Biology

Predisposing aetiologies in Acute Respiratory Distress Syndrome (ARDS), perpetuates to heterogeneous clinical course hampering therapeutic response. Therefore, physiological variables need to be identified by stratifying ARDS subphenotypes and endotype, to target ARDS heterogeneity. The present study is stimulated by the fact that the ARDS heterogeneity arises from diverse pathophysiological changes leading to distinct ARDS endotypes characterized by perturbed biological mechanism which can be exploited in terms of metabolic profile by metabolomics. Biological endotypes using (n = 464 patients and controls), mBALF and serum samples were identified by high – resolution NMR spectroscopy from two clinically diagnosed ARDS subtypes grouped under mild, moderate and severe ARDS as subphenotype1and pulmonary and extra – pulmonary ARDS as subphenotype2. The identified mBALF endotypes (isoleucine, leucine, valine, lysine/arginine, tyrosine, threonine) and serum endotypes (proline, glutamate, phenylalanine, valine) in both subphenotypes by statistical analysis were tested for their reproducibility and robustness. By combining metabolic endotypes with clinical based mortality score (APACHE and SOFA) added to their predictive performance as ARDS mortality predictors. Thus, a comprehensive set of mBALF endotypes representing compartmentalized lung milieu and serological endotypes representing systemic markers of ARDS subtypes were validated. The interlinked biological pathway of these disease specific endotype further elucidated their role as candidate biomarker in governing ARDS heterogeneous biology.

Evolution of ARDS biomarkers: Will metabolomics be the answer?

To date, there is no clinically agreed-upon diagnostic test for acute respiratory distress syndrome (ARDS): the condition is still diagnosed on the basis of a constellation of clinical findings, laboratory tests, and radiological images. Development of ARDS biomarkers has been in a state of continuous flux during the past four decades. To address ARDS heterogeneity, several studies have recently focused on subphenotyping the disease on the basis of observable clinical characteristics and associated blood biomarkers. However, the strong correlation between identified biomarkers and ARDS subphenotypes has yet to establish etiology; hence, there is a need for the adoption of other methodologies for studying ARDS. In this review, we will shed light on ARDS metabolomics research in the literature and discuss advances and major obstacles encountered in ARDS metabolomics research. Generally, the ARDS metabolomics studies focused on identification of differentiating metabolites for diagnosing ARDS, but they were performed to different standards in terms of sample size, selection of control cohort, type of specimens collected, and measuring technique utilized. Virtually none of these studies have been properly validated to identify true metabolomics biomarkers of ARDS. Though in their infancy, metabolomics studies exhibit promise to unfold the biological processes underlying ARDS and, in our opinion, have great potential for pushing forward our present understanding of ARDS.

Histopathologic heterogeneity of acute respiratory distress syndrome revealed by surgical lung biopsy and its clinical implications.

Background/AimsDiffuse alveolar damage (DAD) is the histopathologic hallmark of acute respiratory distress syndrome (ARDS). However, there are several non-DAD conditions mimicking ARDS. The purpose of this study was to investigate the histopathologic heterogeneity of ARDS revealed by surgical lung biopsy and its clinical relevance.MethodsWe retrospectively analyzed 84 patients with ARDS who met the criteria of the Berlin definition and underwent surgical lung biopsy between January 2004 and December 2013 in three academic hospitals in Korea. We evaluated their histopathologic findings and compared the clinical outcomes. Additionally, the impact of surgical lung biopsy on therapeutic alterations was examined.ResultsThe histopathologic findings were highly heterogeneous. Of 84 patients undergoing surgical lung biopsy, DAD was observed in 31 patients (36.9%), while 53 patients (63.1%) did not have DAD. Among the non-DAD patients, diffuse interstitial lung diseases and infections were the most frequent histopathologic findings in 19 and 17 patients, respectively. Although the mortality rate was slightly higher in DAD (71.0%) than in non-DAD (62.3%), the difference was not significant. Overall, the biopsy results led to treatment alterations in 40 patients (47.6%). Patients with non-DAD were more likely to change the treatment than those with DAD (58.5% vs. 29.0%), but there were no significant improvements regarding the mortality rate.ConclusionsThe histopathologic findings of ARDS were highly heterogeneous and classic DAD was observed in one third of the patients who underwent surgical lung biopsy. Although therapeutic alterations were more common in patients with non-DAD-ARDS, there were no significant improvements in the mortality rate.

What's new in ARDS: ARDS also exists in resource-constrained settings.

What's new in ARDS: ARDS also exists in resource-constrained settings.

Use of Lung Ultrasound to Assess the Efficacy of an Alveolar Recruitment Maneuver in Rabbits With Acute Respiratory Distress Syndrome.

To investigate the application of lung ultrasound (US) in the evaluation and implementation of alveolar recruitment maneuvers in acute respiratory distress syndrome (ARDS). Twelve rabbits with saline lavage-induced lung injury were randomly divided into 2 groups: one with alveolar recruitment guided by lung US and the other with alveolar recruitment guided by maximal oxygenation. Recruitment maneuvers were applied according to a stepwise incremental positive end-expiratory pressure method in both groups. In the oxygenation group, a sum of the partial pressures of oxygen and carbon dioxide exceeding 400 mm Hg was used to define adequate recruitment. In the lung US group, a new protocol for reaeration in US-guided lung recruitment was used to guide treatment. Evaluation by lung US, respiratory mechanical parameters, the Smith pathologic score (Crit Care Med 1997; 25:1888-1897), and wet-to-dry ratio were compared between the groups. Opening pressure was significantly higher in the lung US group (mean ± SD, 23.4 ± 3.4 cm H2O) than the oxygenation group (18.7 ± 2.1 cm H2O; P < .05). The reaeration score in the lung US group significantly increased during alveolar recruitment (6.5 ± 1.6 points at baseline versus 13.8 ± 3.0 points after completion; P < .05). Lung compliance, dead space shunts, the Smith pathologic score, and tissue wet-to-dry ratio, however, were not significantly different between the groups. Lung US is an effective means of evaluating and guiding alveolar recruitment in ARDS. Compared with the maximal oxygenation-guided method, the protocol for reaeration in US-guided lung recruitment achieved a higher opening pressure, resulted in greater improvements in lung aeration, and substantially reduced lung heterogeneity in ARDS.