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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pulmonology".

Deadline for manuscript submissions: closed (20 April 2023) | Viewed by 64080

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Special Issue Editors

Prof. Dr. William E. Hurford

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Guest Editor

Department of Anesthesiology, University of Cincinnati, Cincinnati, OH 45267, USA
Interests: acute respiratory failure; mechanical ventilation; trauma; anesthesia and analgesia; safety and quality improvement

Dr. Jesús Villar

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Guest Editor

1. CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, 28029 Madrid, Spain
2. Research Unit, Hospital Universitario Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain
Interests: acute respiratory failure; acute respiratory distress syndrome; mechanical ventilation; sepsis; epidemiological studies and clinical trials

Special Issue Information

Dear Colleagues,

Acute respiratory distress syndrome (ARDS) is a severe, acute lung dysfunction arising from a number of conditions, including severe pneumonia, septicemia, trauma, and also coronavirus disease 2019 (COVID-19) infection.

The aim of this Special Issue of the Journal of Clinical Medicine is to investigate the causes and management or ARDS. We would like to offer a platform for health professions to present the current understanding of ARDS, including the diagnosis, treatment, rehabilitation, and outcomes. Furthermore, research reporting the unfortunate mistakes made during the COVID-19 pandemic that exacerbated ARDS is welcome as well.

Prof. Dr. William E. Hurford
Dr. Jesús Villar
Guest Editors

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Keywords

acute respiratory distress syndrome
acute hypoxic respiratory failure
COVID-19
respiratory failure
ECMO

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Published Papers (9 papers)

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Research

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11 pages, 1291 KiB

Open AccessArticle

Prognostic Value of the Radiographic Assessment of Lung Edema Score in Mechanically Ventilated ICU Patients

by Daan F. L. Filippini, Laura A. Hagens, Nanon F. L. Heijnen, Claudio Zimatore, Leila N. Atmowihardjo, Ronny M. Schnabel, Marcus J. Schultz, Dennis C. J. J. Bergmans, Lieuwe D. J. Bos and Marry R. Smit

J. Clin. Med. 2023, 12(4), 1252; https://doi.org/10.3390/jcm12041252 - 4 Feb 2023

Cited by 1 | Viewed by 2210

Abstract

Introduction: The Radiographic Assessment of Lung Edema (RALE) score provides a semi-quantitative measure of pulmonary edema. In patients with acute respiratory distress syndrome (ARDS), the RALE score is associated with mortality. In mechanically ventilated patients in the intensive care unit (ICU) with respiratory failure not due to ARDS, a variable degree of lung edema is observed as well. We aimed to evaluate the prognostic value of RALE in mechanically ventilated ICU patients. Methods: Secondary analysis of patients enrolled in the ‘Diagnosis of Acute Respiratory Distress Syndrome’ (DARTS) project with an available chest X-ray (CXR) at baseline. Where present, additional CXRs at day 1 were analysed. The primary endpoint was 30-day mortality. Outcomes were also stratified for ARDS subgroups (no ARDS, non-COVID-ARDS and COVID-ARDS). Results: 422 patients were included, of which 84 had an additional CXR the following day. Baseline RALE scores were not associated with 30-day mortality in the entire cohort (OR: 1.01, 95% CI: 0.98–1.03, p = 0.66), nor in subgroups of ARDS patients. Early changes in RALE score (baseline to day 1) were only associated with mortality in a subgroup of ARDS patients (OR: 1.21, 95% CI: 1.02–1.51, p = 0.04), after correcting for other known prognostic factors. Conclusions: The prognostic value of the RALE score cannot be extended to mechanically ventilated ICU patients in general. Only in ARDS patients, early changes in RALE score were associated with mortality. Full article

(This article belongs to the Special Issue New Insights into Acute Respiratory Distress Syndrome)

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Review

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23 pages, 9970 KiB

Open AccessReview

First Stabilize and then Gradually Recruit: A Paradigm Shift in Protective Mechanical Ventilation for Acute Lung Injury

by Gary F. Nieman, David W. Kaczka, Penny L. Andrews, Auyon Ghosh, Hassan Al-Khalisy, Luigi Camporota, Joshua Satalin, Jacob Herrmann and Nader M. Habashi

J. Clin. Med. 2023, 12(14), 4633; https://doi.org/10.3390/jcm12144633 - 12 Jul 2023

Cited by 8 | Viewed by 4800

Abstract

Acute respiratory distress syndrome (ARDS) is associated with a heterogeneous pattern of injury throughout the lung parenchyma that alters regional alveolar opening and collapse time constants. Such heterogeneity leads to atelectasis and repetitive alveolar collapse and expansion (RACE). The net effect is a progressive loss of lung volume with secondary ventilator-induced lung injury (VILI). Previous concepts of ARDS pathophysiology envisioned a two-compartment system: a small amount of normally aerated lung tissue in the non-dependent regions (termed “baby lung”); and a collapsed and edematous tissue in dependent regions. Based on such compartmentalization, two protective ventilation strategies have been developed: (1) a “protective lung approach” (PLA), designed to reduce overdistension in the remaining aerated compartment using a low tidal volume; and (2) an “open lung approach” (OLA), which first attempts to open the collapsed lung tissue over a short time frame (seconds or minutes) with an initial recruitment maneuver, and then stabilize newly recruited tissue using titrated positive end-expiratory pressure (PEEP). A more recent understanding of ARDS pathophysiology identifies regional alveolar instability and collapse (i.e., hidden micro-atelectasis) in both lung compartments as a primary VILI mechanism. Based on this understanding, we propose an alternative strategy to ventilating the injured lung, which we term a “stabilize lung approach” (SLA). The SLA is designed to immediately stabilize the lung and reduce RACE while gradually reopening collapsed tissue over hours or days. At the core of SLA is time-controlled adaptive ventilation (TCAV), a method to adjust the parameters of the airway pressure release ventilation (APRV) modality. Since the acutely injured lung at any given airway pressure requires more time for alveolar recruitment and less time for alveolar collapse, SLA adjusts inspiratory and expiratory durations and inflation pressure levels. The TCAV method SLA reverses the open first and stabilize second OLA method by: (i) immediately stabilizing lung tissue using a very brief exhalation time (≤0.5 s), so that alveoli simply do not have sufficient time to collapse. The exhalation duration is personalized and adaptive to individual respiratory mechanical properties (i.e., elastic recoil); and (ii) gradually recruiting collapsed lung tissue using an inflate and brake ratchet combined with an extended inspiratory duration (4–6 s) method. Translational animal studies, clinical statistical analysis, and case reports support the use of TCAV as an efficacious lung protective strategy. Full article

(This article belongs to the Special Issue New Insights into Acute Respiratory Distress Syndrome)

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21 pages, 2207 KiB

Open AccessReview

Personalized Respiratory Support in ARDS: A Physiology-to-Bedside Review

by Salvatore Lucio Cutuli, Domenico Luca Grieco, Teresa Michi, Melania Cesarano, Tommaso Rosà, Gabriele Pintaudi, Luca Salvatore Menga, Ersilia Ruggiero, Valentina Giammatteo, Giuseppe Bello, Gennaro De Pascale and Massimo Antonelli

J. Clin. Med. 2023, 12(13), 4176; https://doi.org/10.3390/jcm12134176 - 21 Jun 2023

Cited by 10 | Viewed by 4421

Abstract

Acute respiratory distress syndrome (ARDS) is a leading cause of disability and mortality worldwide, and while no specific etiologic interventions have been shown to improve outcomes, noninvasive and invasive respiratory support strategies are life-saving interventions that allow time for lung recovery. However, the inappropriate management of these strategies, which neglects the unique features of respiratory, lung, and chest wall mechanics may result in disease progression, such as patient self-inflicted lung injury during spontaneous breathing or by ventilator-induced lung injury during invasive mechanical ventilation. ARDS characteristics are highly heterogeneous; therefore, a physiology-based approach is strongly advocated to titrate the delivery and management of respiratory support strategies to match patient characteristics and needs to limit ARDS progression. Several tools have been implemented in clinical practice to aid the clinician in identifying the ARDS sub-phenotypes based on physiological peculiarities (inspiratory effort, respiratory mechanics, and recruitability), thus allowing for the appropriate application of personalized supportive care. In this narrative review, we provide an overview of noninvasive and invasive respiratory support strategies, as well as discuss how identifying ARDS sub-phenotypes in daily practice can help clinicians to deliver personalized respiratory support and potentially improve patient outcomes. Full article

(This article belongs to the Special Issue New Insights into Acute Respiratory Distress Syndrome)

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20 pages, 1357 KiB

Open AccessReview

Genetic Determinants of the Acute Respiratory Distress Syndrome

by Eva Suarez-Pajes, Eva Tosco-Herrera, Melody Ramirez-Falcon, Silvia Gonzalez-Barbuzano, Tamara Hernandez-Beeftink, Beatriz Guillen-Guio, Jesús Villar and Carlos Flores

J. Clin. Med. 2023, 12(11), 3713; https://doi.org/10.3390/jcm12113713 - 27 May 2023

Cited by 3 | Viewed by 4107

Abstract

Acute respiratory distress syndrome (ARDS) is a life-threatening lung condition that arises from multiple causes, including sepsis, pneumonia, trauma, and severe coronavirus disease 2019 (COVID-19). Given the heterogeneity of causes and the lack of specific therapeutic options, it is crucial to understand the genetic and molecular mechanisms that underlie this condition. The identification of genetic risks and pharmacogenetic loci, which are involved in determining drug responses, could help enhance early patient diagnosis, assist in risk stratification of patients, and reveal novel targets for pharmacological interventions, including possibilities for drug repositioning. Here, we highlight the basis and importance of the most common genetic approaches to understanding the pathogenesis of ARDS and its critical triggers. We summarize the findings of screening common genetic variation via genome-wide association studies and analyses based on other approaches, such as polygenic risk scores, multi-trait analyses, or Mendelian randomization studies. We also provide an overview of results from rare genetic variation studies using Next-Generation Sequencing techniques and their links with inborn errors of immunity. Lastly, we discuss the genetic overlap between severe COVID-19 and ARDS by other causes. Full article

(This article belongs to the Special Issue New Insights into Acute Respiratory Distress Syndrome)

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16 pages, 316 KiB

Open AccessEditor’s ChoiceReview

Corticosteroids in ARDS

by Emmanuelle Kuperminc, Nicholas Heming, Miguel Carlos and Djillali Annane

J. Clin. Med. 2023, 12(9), 3340; https://doi.org/10.3390/jcm12093340 - 8 May 2023

Cited by 10 | Viewed by 10426

Abstract

Acute respiratory distress syndrome (ARDS) is frequently associated with sepsis. ARDS and sepsis exhibit a common pathobiology, namely excessive inflammation. Corticosteroids are powerful anti-inflammatory agents that are routinely used in septic shock and in oxygen-dependent SARS-CoV-2 related acute respiratory failure. Recently, corticosteroids were found to reduce mortality in severe community-acquired pneumonia. Corticosteroids may therefore also have a role to play in the treatment of ARDS. This narrative review was undertaken following a PubMed search for English language reports published before January 2023 using the terms acute respiratory distress syndrome, sepsis and steroids. Additional reports were identified by examining the reference lists of selected articles and based on personnel knowledge of the authors of the field. High-quality research is needed to fully understand the role of corticosteroids in the treatment of ARDS and to determine the optimal timing, dosing and duration of treatment. Full article

(This article belongs to the Special Issue New Insights into Acute Respiratory Distress Syndrome)

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12 pages, 296 KiB

Open AccessReview

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

by Alicia N. Rizzo, Neil R. Aggarwal, B. Taylor Thompson and Eric P. Schmidt

J. Clin. Med. 2023, 12(4), 1563; https://doi.org/10.3390/jcm12041563 - 16 Feb 2023

Cited by 10 | Viewed by 3274

Abstract

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. Full article

(This article belongs to the Special Issue New Insights into Acute Respiratory Distress Syndrome)

25 pages, 1120 KiB

Open AccessReview

Challenges in ARDS Definition, Management, and Identification of Effective Personalized Therapies

by Denise Battaglini, Brigitta Fazzini, Pedro Leme Silva, Fernanda Ferreira Cruz, Lorenzo Ball, Chiara Robba, Patricia R. M. Rocco and Paolo Pelosi

J. Clin. Med. 2023, 12(4), 1381; https://doi.org/10.3390/jcm12041381 - 9 Feb 2023

Cited by 25 | Viewed by 26849

Abstract

Over the last decade, the management of acute respiratory distress syndrome (ARDS) has made considerable progress both regarding supportive and pharmacologic therapies. Lung protective mechanical ventilation is the cornerstone of ARDS management. Current recommendations on mechanical ventilation in ARDS include the use of low tidal volume (V_T) 4–6 mL/kg of predicted body weight, plateau pressure (P_PLAT) < 30 cmH₂O, and driving pressure (∆P) < 14 cmH₂O. Moreover, positive end-expiratory pressure should be individualized. Recently, variables such as mechanical power and transpulmonary pressure seem promising for limiting ventilator-induced lung injury and optimizing ventilator settings. Rescue therapies such as recruitment maneuvers, vasodilators, prone positioning, extracorporeal membrane oxygenation, and extracorporeal carbon dioxide removal have been considered for patients with severe ARDS. Regarding pharmacotherapies, despite more than 50 years of research, no effective treatment has yet been found. However, the identification of ARDS sub-phenotypes has revealed that some pharmacologic therapies that have failed to provide benefits when considering all patients with ARDS can show beneficial effects when these patients were stratified into specific sub-populations; for example, those with hyperinflammation/hypoinflammation. The aim of this narrative review is to provide an overview on current advances in the management of ARDS from mechanical ventilation to pharmacological treatments, including personalized therapy. Full article

(This article belongs to the Special Issue New Insights into Acute Respiratory Distress Syndrome)

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17 pages, 1053 KiB

Open AccessReview

Respiratory Subsets in Patients with Moderate to Severe Acute Respiratory Distress Syndrome for Early Prediction of Death

by Jesús Villar, Cristina Fernández, Jesús M. González-Martín, Carlos Ferrando, José M. Añón, Ana M. del Saz-Ortíz, Ana Díaz-Lamas, Ana Bueno-González, Lorena Fernández, Ana M. Domínguez-Berrot, Eduardo Peinado, David Andaluz-Ojeda, Elena González-Higueras, Anxela Vidal, M. Mar Fernández, Juan M. Mora-Ordoñez, Isabel Murcia, Concepción Tarancón, Eleuterio Merayo, Alba Pérez, Miguel A. Romera, Francisco Alba, David Pestaña, Pedro Rodríguez-Suárez, Rosa L. Fernández, Ewout W. Steyerberg, Lorenzo Berra, Arthur S. Slutsky and The Spanish Initiative for Epidemiology, Stratification and Therapies of ARDS (SIESTA) Network Show full author list Hide full author list

J. Clin. Med. 2022, 11(19), 5724; https://doi.org/10.3390/jcm11195724 - 27 Sep 2022

Cited by 6 | Viewed by 2669

Abstract

Introduction: In patients with acute respiratory distress syndrome (ARDS), the PaO₂/FiO₂ ratio at the time of ARDS diagnosis is weakly associated with mortality. We hypothesized that setting a PaO₂/FiO₂ threshold in 150 mm Hg at 24 h from moderate/severe ARDS diagnosis would improve predictions of death in the intensive care unit (ICU). Methods: We conducted an ancillary study in 1303 patients with moderate to severe ARDS managed with lung-protective ventilation enrolled consecutively in four prospective multicenter cohorts in a network of ICUs. The first three cohorts were pooled (n = 1000) as a testing cohort; the fourth cohort (n = 303) served as a confirmatory cohort. Based on the thresholds for PaO₂/FiO₂ (150 mm Hg) and positive end-expiratory pressure (PEEP) (10 cm H₂O), the patients were classified into four possible subsets at baseline and at 24 h using a standardized PEEP-FiO₂ approach: (I) PaO₂/FiO₂ ≥ 150 at PEEP < 10, (II) PaO₂/FiO₂ ≥ 150 at PEEP ≥ 10, (III) PaO₂/FiO₂ < 150 at PEEP < 10, and (IV) PaO₂/FiO₂ < 150 at PEEP ≥ 10. Primary outcome was death in the ICU. Results: ICU mortalities were similar in the testing and confirmatory cohorts (375/1000, 37.5% vs. 112/303, 37.0%, respectively). At baseline, most patients from the testing cohort (n = 792/1000, 79.2%) had a PaO₂/FiO₂ < 150, with similar mortality among the four subsets (p = 0.23). When assessed at 24 h, ICU mortality increased with an advance in the subset: 17.9%, 22.8%, 40.0%, and 49.3% (p < 0.0001). The findings were replicated in the confirmatory cohort (p < 0.0001). However, independent of the PEEP levels, patients with PaO₂/FiO₂ < 150 at 24 h followed a distinct 30-day ICU survival compared with patients with PaO₂/FiO₂ ≥ 150 (hazard ratio 2.8, 95% CI 2.2–3.5, p < 0.0001). Conclusions: Subsets based on PaO₂/FiO₂ thresholds of 150 mm Hg assessed after 24 h of moderate/severe ARDS diagnosis are clinically relevant for establishing prognosis, and are helpful for selecting adjunctive therapies for hypoxemia and for enrolling patients into therapeutic trials. Full article

(This article belongs to the Special Issue New Insights into Acute Respiratory Distress Syndrome)

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7 pages, 241 KiB

Open AccessPerspective

Newly Proposed Diagnostic Criteria for Acute Respiratory Distress Syndrome: Does Inclusion of High Flow Nasal Cannula Solve the Problem?

by Rong Liufu, Chun-Yao Wang, Li Weng and Bin Du

J. Clin. Med. 2023, 12(3), 1043; https://doi.org/10.3390/jcm12031043 - 29 Jan 2023

Cited by 4 | Viewed by 3451

Abstract

Acute respiratory distress syndrome (ARDS) is a common life-threatening clinical syndrome which accounts for 10% of intensive care unit admissions. Since the Berlin definition was developed, the clinical diagnosis and therapy have changed dramatically by adding a minimum positive end-expiratory pressure (PEEP) to the assessment of hypoxemia compared to the American-European Consensus Conference (AECC) definition in 1994. High-flow nasal cannulas (HFNC) have become widely used as an effective respiratory support for hypoxemia to the extent that their use was proposed in the expansion of the ARDS criteria. However, there would be problems if the diagnosis of a specific disease or clinical syndrome occurred, based on therapeutic strategies. Full article

(This article belongs to the Special Issue New Insights into Acute Respiratory Distress Syndrome)

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