• Apoptosis
• Curcumin
• Heatstroke
• Lung injury
• Network pharmacology

• Animals
• Curcumin/pharmacology
• Curcumin/therapeutic use
• Proto-Oncogene Proteins c-akt/metabolism
• Molecular Docking Simulation
• Male
• Mice
• Signal Transduction/drug effects
• Lung Injury/drug therapy
• Lung Injury/etiology
• Lung Injury/pathology
• Lung Injury/metabolism
• Heat Stroke/complications
• Heat Stroke/drug therapy
• Lung/drug effects
• Lung/ultrastructure
• Lung/pathology
• Phosphatidylinositol 3-Kinases/metabolism
• Disease Models, Animal
• Caspase 3/metabolism

• 82371889 National Natural Science Foundation of China General Program
• 2020D04015 Open Project of Key Laboratory of Xinjiang Uygur Autonomous Region

• ARDS
• Cytokines
• Glucocorticoids
• Immune responses
• Inflammation
• Phenotypes
• Pneumonia

• IK2 BX004886 BLRD VA
• R03 HL162655 NIH HHS
• P01 HL114453 NHLBI NIH HHS
• R03 HL162655 NHLBI NIH HHS
• K23 GM122069 NIGMS NIH HHS
• National Institutes of Health (US)
• NHLBI Division of Intramural Research
• National Institutes of Health
• Biomedical Laboratory Research and Development, VA Office of Research and Development

• Escherichia coli
• Toll-like receptor 4
• bacterial phagocytosis
• host defense
• inflammation
• surfactant protein A-derived peptide

• Humans
• Toll-Like Receptor 4/metabolism
• Escherichia coli/metabolism
• Histones
• Tumor Necrosis Factor-alpha/metabolism
• Calnexin/metabolism
• Inflammation/metabolism
• Endoplasmic Reticulum/metabolism
• Lipopolysaccharides/pharmacology

• R01 HL136325 NHLBI NIH HHS
• R01 HL136325 NHLBI NIH HHS
• American Heart Association (AHA)
• HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)

• Gossypin
• acute lung injury
• dexamethasone
• oleic acid
• oxidative stress

• Humans
• COVID-19/complications
• SARS-CoV-2
• Prospective Studies
• Critical Illness
• Pneumonia, Ventilator-Associated/drug therapy
• COVID-19 Drug Treatment
• Respiratory Distress Syndrome
• Methylprednisolone/therapeutic use
• Adrenal Cortex Hormones/therapeutic use
• Dexamethasone/therapeutic use

• Acute respiratory distress syndrome
• corticosteroids
• covid-19
• inhaled nitric oxide
• neuromuscular blocking drugs
• pediatric ards
• pheno-endotypes
• surfactant replacement therapy

• Adrenal Cortex Hormones
• Child
• Forecasting
• Graft vs Host Disease
• Humans
• Respiration, Artificial
• Respiratory Distress Syndrome/drug therapy

• Adrenal Cortex Hormones/therapeutic use
• Cohort Studies
• Critical Care
• Humans
• Meta-Analysis as Topic
• Respiration, Artificial
• Respiratory Distress Syndrome/drug therapy

• ARDS
• ICU mortality
• glucocorticoids
• joint model
• marginal structural cox model

Patients with influenza infection may develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. Some patients with ARDS receiving extracorporeal membrane oxygenation (ECMO) support die of infectious complications. We aimed to investigate the risk factors affecting the clinical outcomes in critically ill patients with influenza. We retrospectively reviewed the medical records of influenza patients between January 2006 and May 2016 at the Kaohsiung Veterans General Hospital in Taiwan. Patients aged below 20 years or without laboratory-confirmed influenza were excluded. Critically ill patients who presented with ARDS (P = 0.004, odds ratio (OR): 8.054, 95% confidence interval (CI): 1.975–32.855), a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.008, OR: 1.102, 95% CI: 1.025–1.184), or higher positive end-expiratory pressure (P = 0.008, OR: 1.259, 95% CI: 1.061–1.493) may have a higher risk of receiving ECMO. Influenza A (P = 0.037, OR: 0.105, 95% CI: 0.013–0.876) and multiple organ failure (P = 0.007, OR: 0.056, 95% CI: 0.007–0.457) were significantly associated with higher mortality rates. In conclusion, our study showed critically ill influenza patients with ARDS, higher APACHE II scores, and higher positive end-expiratory pressure have a higher risk of receiving ECMO support. Influenza A and multiple organ failure are predictors of mortality.

• acute respiratory distress syndrome
• extracorporeal membrane oxygenation
• multiple organ failure
• outcome
• severe influenza

• glucocorticoids inflammation covid-19

• Anti-Inflammatory Agents/therapeutic use
• Glucocorticoids/therapeutic use
• Humans
• Immunosuppressive Agents/therapeutic use
• Respiratory Distress Syndrome/drug therapy
• Respiratory Distress Syndrome/virology
• SARS-CoV-2
• COVID-19 Drug Treatment

• The Deutsche Forschungsgemeinschaft SFB-TRR 205 to V.I.A. & HE 8391/1-1 to H.H.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2), is still a global public health problem for humans. It has caused more than 10,000,000 infections and more than 500,000 deaths in the world so far. Many scientists have tried their best to discover safe and effective drugs for the treatment of this disease; however, there are still no approved standard therapeutics or effective antiviral drugs on the market. Many new drugs are being developed, and several traditional drugs that were originally indicated or proposed for other diseases are likely to be effective in treating COVID-19, but their safety and efficacy are controversial, under study, or in clinical trial phases. Fortunately, some novel antiviral strategies, such as convalescent plasma, clustered regularly interspaced short palindromic repeats (CRISPR), and mesenchymal stem cell (MSC) therapy, potentially offer an additional or alternative option or compassionate use for the people suffering from COVID-19, especially for critically ill patients, although their safety and efficacy are also under study. In this review, we explore the applications, possible mechanisms, and efficacy in successful cases using convalescent plasma, CRISPR, and MSC therapy for COVID-19 treatment, respectively. Furthermore, the perspectives and limitations of these novel antiviral strategies are evaluated.

• COVID-19
• CRISPR
• SARS–CoV-2
• compassionate use
• convalescent plasma
• coronaviruses
• mesenchymal stem cell therapy

Pneumocystis jirovecii is recognized as an opportunistic pathogen in immunosuppressed patients. We report a case of severe Pneumocystis pneumonia (PCP) in an infant with acquired combined immunodeficiency secondary to maternal chemotherapy exposure during the second and third trimesters of pregnancy. The infant required cardiorespiratory support with veno-venous extracorporeal membrane oxygenation (VV-ECMO) for severe respiratory failure. This case highlights the potential for severe acquired immunodeficiency in this patient cohort and further postnatal surveillance is highly recommended.

• ARDS
• bosentan
• pharmacological treatment

• Acute pulmonary inflammation
• Acute respiratory distress syndrome
• Critical illness
• Diagnosis
• Inflammatory biomarkers
• Pneumonia
• Treatment

Acute lung injury (ALI) is the most serious pulmonary complication after lung resection. Although the beneficial effects of low-dose corticosteroids have been demonstrated in patients with postoperative ALI, there are limited data on optimal corticosteroid treatment.

We retrospectively analyzed 58 patients who were diagnosed with ALI among 7593 patients who underwent lung cancer surgery between January 2009 and December 2016.

Of the 58 patients, 42 (72%) received corticosteroid treatment within 72 h (early treatment group) and 16 (28%) received corticosteroid treatment more than 72 h after ALI occurred (late treatment group). The early treatment group demonstrated a higher response to corticosteroid treatment compared with the late treatment group (95% versus 69%, respectively, p = 0.014), had an improved lung injury score (86% versus 63%, p = 0.072), and were more likely to be successfully weaned from the ventilator within 7 days (57% versus 39%, p = 0.332). During corticosteroid treatment, the early treatment group had a lower rate of delirium (24% versus 63%, p = 0.012) compared with the late treatment group. No significant differences in length of stay (30 versus 37 days, p = 0.254) or in-hospital mortality (43% versus 38%, p = 0.773) were observed; however, the early treatment group tended to have a higher rate of successful weaning than the late treatment group (p = 0.098, log-rank test).

Early initiation of corticosteroid treatment improved lung injury and promoted ventilator weaning in patients with ALI following lung resection for lung cancer.

• acute lung injury
• acute respiratory distress syndrome
• glucocorticoid
• lung neoplasm
• operative procedure

Lung fibroproliferation in ARDS patients is associated with mortality. Alveolar procollagen III (NT-PCP-III) is a validated biomarker of lung fibroproliferation. A chest CT scan could be useful for the diagnosis of lung fibroproliferation. The aim of this study was to identify lung fibroproliferative CT scan aspects in ARDS patients with high levels of NT-PCP-III.

This retrospective study included ARDS patients who had at least one assessment of alveolar NT-PCP-III and a chest CT scan within 3 days before or after NT-PCP-III determination. An alveolar level of NT-PCP-III > 9 µG/L indicated fibroproliferation. The CT scan was scored on interstitial and alveolar abnormalities. Each lobe was scored from 0 to 5 according to the severity of the abnormalities. The crude score and the corrected score (related to the number of scored lobes in cases of important lobar condensation or lobectomy) were used. One hundred ninety-two patients were included, for a total of 228 alveolar NT-PCP-III level and CT scan ‘couples’. Crude and corrected CT scan fibrosis scores were higher in the fibroproliferation group compared with the no fibroproliferation group (crude score: 12 [9–17] vs 14 [11–12], p = 0.002; corrected score: 2.8 [2.2–4.0] vs 3.4 [2.5–4.7], p < 0.001). CT scan fibrosis scores and NT-PCP-III levels were significantly but weakly correlated (crude score: ρ = 0.178, p = 0.007; corrected score: ρ = 0.184, p = 0.005).

When the alveolar level of NT-PCP-III was used as a surrogate marker of histological lung fibroproliferation, the CT scan fibrosis score was significantly higher in patients with active lung fibroproliferation. Pulmonary condensation is the main limitation to diagnosing fibroproliferation during ARDS.

The online version of this article (10.1186/s13613-019-0516-9) contains supplementary material, which is available to authorized users.

• Acute respiratory distress syndrome
• CT scan
• Fibroproliferation
• Lung fibrosis
• Procollagen
• Scoring

Changes in tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10 and vascular endothelial growth factor (VEGF) in serum and bronchoalveolar lavage fluid (BALF) in rats with acute respiratory distress syndrome (ARDS) and the intervention effect of dexamethasone were observed to explore the theoretical basis of dexamethasone in the treatment of ARDS. Seventy-two rats were randomly divided into normal control group (group N, n=24), ARDS model group (group L, n=24) and dexamethasone group (group D, n=24). The ARDS rat model was established by jointly injecting oleic acid and lipopolysaccharide via the caudal vein, while rats in group D received intervention with dexamethasone. The wet/dry weight ratios of lung tissues were measured, and the levels of TNF-α, IL-6, IL-10 and VEGF in serum and BALF were measured via enzyme-linked immunosorbent assay. The wet/dry weight ratio of lung tissues of rats in group D was significantly decreased compared with that in group L (P<0.05 or P<0.01). The levels of TNF-α, IL-6 and VEGF in serum and BALF of rats in group L and D were obviously increased compared with those in group N at each time point (P<0.01). The levels of TNF-α, IL-6 and VEGF in serum and BALF of rats in group D were significantly decreased compared with those in group L (P<0.01). In conclusion, there is a serious imbalance between anti-inflammatory response and inflammatory response in rats with ARDS induced by oleic acid combined with lipopolysaccharide of Escherichia coli, whereas dexamethasone can alleviate lung injury through inhibiting expression levels of inflammatory factors and promoting expression levels of anti-inflammatory factors.

• acute respiratory distress syndrome
• cytokines
• dexamethasone

• NETosis
• acute respiratory distress syndrome
• sepsis
• vascular permeability

• Animals
• Capillary Permeability
• Endothelium, Vascular/metabolism
• Humans
• Respiratory Distress Syndrome/drug therapy
• Respiratory Distress Syndrome/etiology
• Respiratory Distress Syndrome/immunology
• Signal Transduction

Human respiratory syncytial virus usually causes self-limiting upper respiratory infection and occasionally causes pneumonia in immunocompromised hosts. Respiratory syncytial virus-induced severe pneumonia or acute respiratory distress syndrome in immunocompetent adults has been rarely described. Unfortunately, optimal treatment has not been established for this potentially fatal condition. We report a case of respiratory syncytial virus-induced acute respiratory distress syndrome occurring in a previously healthy man successfully treated with orally administered ribavirin.

An 81-year-old previously healthy Korean man presented with cough, dyspnea, and febrile sensation. He had hypoxemia with diffuse ground glass opacity evident on chest radiography, which progressed and required mechanical ventilation. All microbiological tests were negative except multiplex real-time reverse transcriptase polymerase chain reaction using respiratory specimen, which was positive for human adenovirus. Under the diagnosis of respiratory syncytial virus-induced acute respiratory distress syndrome, orally administered ribavirin was administered and he recuperated completely without complications.

This case demonstrates the potential usefulness of orally administered ribavirin as a therapeutic option for severe respiratory syncytial virus infection, at least in an immunocompetent host.

• Acute respiratory distress syndrome
• Case report
• Respiratory syncytial virus
• Ribavirin

• ARDS
• Acute lung injury
• clinical practice guideline
• systematic review

The efficacy of corticosteroid use in acute respiratory distress syndrome (ARDS) remains controversial. Generally, short-term high-dose corticosteroid therapy is considered to be ineffective in ARDS. On the other hand, low-dose, long-term use of corticosteroids has been reported to be effective since they provide continued inhibition of the systemic inflammatory response syndrome (SIRS) that accompanies ARDS. Thus far, no reports have been published on the efficacy of initiating treatment with a high-dose corticosteroid regimen with tapering.

We conducted a retrospective observational study involving 186 patients treated at a teaching hospital (68% had sepsis, pneumonia, or aspiration pneumonia). ARDS was diagnosed according to the Berlin definition. Patients were divided into a high-dose (n = 21) or low-dose corticosteroid group (n = 165) to compare the effectiveness of a down-titration regimen. The primary medical team chose which treatment a patient would receive. We were careful to conduct a differential diagnosis of interstitial pneumonia (e.g., acute eosinophilic pneumonia) since corticosteroid treatment has been proven effective in that patient population. The primary outcome was the 60-day mortality rate. The secondary outcome was the number of ventilator-free days (VFD).

Those started on a high-dose regimen had a significantly higher 60-day mortality rate (P = 0.031) with significantly fewer VFD (P = 0.021). Propensity scores were used to adjust patient backgrounds in a variable analysis that also showed the high-dose regimen was a factor in decreasing VFD (OR, 95.63; 95% CI, 1.74–5271.07; P = 0.026) and worsening the 60-day mortality rate (OR, 2.54; 95% CI, 0.92–7.02; P = 0.072).

A tapering regimen after high-dose corticosteroids is likely to increase ventilator dependency and might aggravate the prognosis of patients with ARDS diagnosed according to the Berlin definition.

• Acute respiratory distress syndrome
• High-dose corticosteroid therapy
• Mortality

We describe a case of severe refractory hypoxemia requiring prolonged extra corporeal membrane oxygenation (ECMO) support in a case of postpartum acute respiratory distress syndrome (ARDS). The clinical course was marked by persistently poor lung compliance and several complications of ECMO, that is, significant hemolysis, hemothorax, and intracranial bleeding. We report marked improvement of lung mechanics and respiratory function, leading to accelerated separation from ECMO, following rescue administration of low dose methylprednisolone 24 days after the onset of ARDS. Corticosteroid treatment was safe and well tolerated. In contrast with the conclusions of the 2006 ARDS Network trial, our report establishes a case in support of the use of low dose methylprednisolone as a safe and effective rescue treatment option in selected subsets of patients with nonresolving ARDS.

• Acute respiratory distress syndrome
• Corticosteroids
• Intensive care unit
• Mortality
• Sepsis

• acute respiratory distress syndrome
• coagulation
• dexamethasone
• lung
• pneumonia

• Adult
• Antithrombin III/chemistry
• Blood Coagulation
• Blood Coagulation Disorders/drug therapy
• Bronchoalveolar Lavage
• Bronchoalveolar Lavage Fluid
• Dexamethasone/pharmacology
• Double-Blind Method
• Endotoxins/adverse effects
• Female
• Glucocorticoids/pharmacology
• Healthy Volunteers
• Humans
• Inflammation
• Lung/drug effects
• Male
• Peptide Hydrolases/chemistry
• Thrombosis
• Young Adult

• Practice Guideline
• Respiration, Artificial
• Respiratory Distress Syndrome, Acute
• Respiratory Distress Syndrome, Adult
• Ventilators, Mechanical

• Acute respiratory distress syndrome
• Mechanical ventilation
• Pathophysiology
• Prone position
• Ventilator-induced lung injury

• ventilator-induced lung injury
• dexamethasone
• respiratory distress syndrome, adult

• Animals
• Blood Gas Analysis
• Dexamethasone/therapeutic use
• Glucocorticoids/therapeutic use
• Leukocyte Count
• Lung/pathology
• Male
• Models, Animal
• Rats, Wistar
• Reference Values
• Reproducibility of Results
• Time Factors
• Treatment Outcome
• Ventilator-Induced Lung Injury/prevention & control

Innate immunity normally provides excellent defence against invading microorganisms. Acute inflammation is a form of innate immune defence and represents one of the primary responses to injury, infection and irritation, largely mediated by granulocyte effector cells such as neutrophils and eosinophils. Failure to remove an inflammatory stimulus (often resulting in failed resolution of inflammation) can lead to chronic inflammation resulting in tissue injury caused by high numbers of infiltrating activated granulocytes. Successful resolution of inflammation is dependent upon the removal of these cells. Under normal physiological conditions, apoptosis (programmed cell death) precedes phagocytic recognition and clearance of these cells by, for example, macrophages, dendritic and epithelial cells (a process known as efferocytosis). Inflammation contributes to immune defence within the respiratory mucosa (responsible for gas exchange) because lung epithelia are continuously exposed to a multiplicity of airborne pathogens, allergens and foreign particles. Failure to resolve inflammation within the respiratory mucosa is a major contributor of numerous lung diseases. This review will summarise the major mechanisms regulating lung inflammation, including key cellular interplays such as apoptotic cell clearance by alveolar macrophages and macrophage/neutrophil/epithelial cell interactions. The different acute and chronic inflammatory disease states caused by dysregulated/impaired resolution of lung inflammation will be discussed. Furthermore, the resolution of lung inflammation during neutrophil/eosinophil-dominant lung injury or enhanced resolution driven via pharmacological manipulation will also be considered.

• Apoptosis
• ETosis
• Efferocytosis
• Eosinophils
• Lung diseases
• Lung inflammation
• Macrophages
• Neutrophils
• Pro-resolution mediators

• hypoxemia
• refractory
• respiratory distress

• acute respiratory distress syndrome
• glucocorticoid treatment
• mechanical ventilation
• survival

• acute respiratory distress syndrome
• glucocorticoid treatment
• intensive care unit-acquired weakness
• mechanical ventilation
• muscle weakness
• steroids
• survival

• ARDS
• Chemokines
• Cytokines
• Glucocorticoids
• Inflammation
• Lung injury
• Mediators
• Pediatrics
• Steroids

• Acute Disease
• Adolescent
• Biomarkers/blood
• C-Reactive Protein/metabolism
• Child
• Child, Preschool
• Cytokines/blood
• Double-Blind Method
• Female
• Glucocorticoids/administration & dosage
• Glucocorticoids/therapeutic use
• Humans
• Infant
• Infant, Newborn
• Inflammation Mediators/blood
• Infusions, Intravenous
• Lung Diseases/blood
• Lung Diseases/drug therapy
• Male
• Methylprednisolone/administration & dosage
• Methylprednisolone/therapeutic use
• Pilot Projects
• Prognosis
• Regression Analysis
• Treatment Outcome

• R01 AI090059 NIAID NIH HHS
• R01ES015050 NIEHS NIH HHS
• HL118118-01A1 NHLBI NIH HHS
• P42 ES013648 NIEHS NIH HHS
• P42ES013648 NIEHS NIH HHS
• R01 ES015050 NIEHS NIH HHS
• K08 HL118118 NHLBI NIH HHS
• R01AI090059 NIAID NIH HHS

• ARDS
• Ang-2
• ICAM-1
• MMP-8
• biomarker
• methylprednisolone
• pediatric
• sRAGE

• Adult respiratory distress syndrome
• Glucocorticoid treatment
• Mechanical ventilation
• Survival

Acute respiratory failure contributes significantly to nonrelapse mortality after allogeneic hematopoietic stem cell transplantation. Although there is a trend of improved survival over time, mortality remains unacceptably high. An understanding of the pathophysiology of early respiratory failure, opportunities for targeted therapy, assessment of the patient at risk, optimal use of noninvasive positive pressure ventilation, strategies to improve alveolar recruitment, appropriate fluid management, care of the patient with chronic lung disease, and importantly, a team approach between critical care and transplantation services may improve outcomes.

•

Outcomes from acute respiratory failure after hematopoietic stem cell transplantation remain unacceptably high.

• Respiratory failure
• Transplantation

• acute lung injury/acute respiratory distress syndrome
• glucocorticoids
• metyrapone
• sepsis

• Corticosteroids
• Cough
• Fever
• Hoarseness

• Adrenal Cortex Hormones/adverse effects
• Adrenal Cortex Hormones/therapeutic use
• Adult
• Cardiovascular Agents/therapeutic use
• Comorbidity
• Glucocorticoids/adverse effects
• Glucocorticoids/therapeutic use
• Humans
• Observational Studies as Topic
• Odds Ratio
• Respiratory Distress Syndrome/drug therapy
• Respiratory Distress Syndrome/mortality
• Respiratory Distress Syndrome/physiopathology
• Treatment Outcome

• Aged
• Biomarkers/metabolism
• Biopsy
• Bronchoalveolar Lavage Fluid/chemistry
• Collagen Type III/metabolism
• Female
• Fibroblasts/pathology
• Glucocorticoids/therapeutic use
• Humans
• Male
• Middle Aged
• Prospective Studies
• Pulmonary Fibrosis/drug therapy
• Pulmonary Fibrosis/etiology
• Pulmonary Fibrosis/metabolism
• Respiratory Distress Syndrome/complications
• Respiratory Distress Syndrome/metabolism

• ARDS
• Corticosteroids
• Outcomes
• Prevention
• Treatment

• Drug Administration Schedule
• Glucocorticoids/administration & dosage
• Humans
• Respiratory Distress Syndrome/drug therapy

• K23 HL074294 NHLBI NIH HHS
• N01HR46055 NHLBI NIH HHS
• T32 HL007287 NHLBI NIH HHS
• T32 HL 007287 NHLBI NIH HHS

• acute respiratory distress syndrome
• children
• nitric oxide
• pediatric
• prone positioning
• prostaglandin
• pulmonary hypertension
• steroid
• surfactant