Biomarkers, signaling pathways, and programmed cell death in acute lung injury and its treatment with Traditional Chinese Medicine: a narrative review.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common life-threatening, high-mortality lung diseases associated with acute and severe inflammation of the lungs. However, research on diagnostic markers and signaling pathways associated with ALI/ARDS is lacking, and no specific drug therapy is available for ALI/ARDS. Therefore, in this study, biomarkers and signaling pathways associated with ALI/ARDS were summarized to provide a reference for future clinical and research work. A review of Traditional Chinese Medicine for the treatment or prevention of ALI/ARDS is also presented to provide a reference for further development of Traditional Chinese Medicine. In summary, this review will help raise awareness of ALI/ARDS and provide insight into the future exploitation of Traditional Chinese Medicine.

[Therapy of coronavirus disease 2019 induced acute respiratory distress syndrome is different from traditional acute respiratory distress syndrome].

Coronavirus disease 2019 (COVID-19) has become a global public health emergency threatening people's lives around the world. Although the acute respiratory distress syndrome (ARDS) induced by COVID-19 is similar to the ARDS caused by other diseases in terms of pathophysiological basis and clinical manifestations, they are also different in many aspects, which lead to different clinical therapies. Therefore, understanding the differences and similarities of ARDS induced by COVID-19 and other diseases currently are the basis for clinicians to make decisions for the treatment of COVID-19 induced ARDS.

Respiratory conditions in coronavirus disease 2019 (COVID-19): Important considerations regarding novel treatment strategies to reduce mortality.

A novel virus named 2019 novel coronavirus (2019-nCoV/SARS-CoV-2) causes symptoms that are classified as coronavirus disease (COVID-19). Respiratory conditions are extensively described among more serious cases of COVID-19, and the onset of acute respiratory distress syndrome (ARDS) is one of the hallmark features of critical COVID-19 cases. ARDS can be directly life-threatening because it is associated with low blood oxygenation levels and can result in organ failure. There are no generally recognized effective treatments for COVID-19, but treatments are urgently needed. Anti-viral medications and vaccines are in the early developmental stages and may take many months or even years to fully develop. At present, management of COVID-19 with respiratory and ventilator support are standard therapeutic treatments, but unfortunately such treatments are associated with high mortality rates. Therefore, it is imperative to consider novel new therapeutic interventions to treat/ameliorate respiratory conditions associated with COVID-19. Alternate treatment strategies utilizing clinically available treatments such as hyperbaric oxygen therapy (HBOT), packed red blood cell (pRBC) transfusions, or erthropoiesis-stimulating agent (ESA) therapy were hypothesized to increase oxygenation of tissues by alternative means than standard respiratory and ventilator treatments. It was also revealed that alternative treatments currently being considered for COVID-19 such as chloroquine and hydroxychloroquine by increasing hemoglobin production and increasing hemoglobin availability for oxygen binding and acetazolamine (for the treatment of altitude sickness) by causing hyperventilation with associated increasing levels of oxygen and decreasing levels of carbon dioxide in the blood may significantly ameliorate COVID-19 respiratory symptoms. In conclusion, is recommend, given HBOT, pRBC, and ESA therapies are currently available and routinely utilized in the treatment of other conditions, that such therapies be tried among COVID-19 patients with serious respiratory conditions and that future controlled-clinical trials explore the potential usefulness of such treatments among COVID-19 patients with respiratory conditions.

A 55-Year-Old Man With Cough and Hematochezia.

CASE PRESENTATION: A 55-year-old man presented to the ED with a 3-week history of worsening cough and shortness of breath. He had blood-tinged sputum, fever, night sweats, and a 2.7 kg weight loss within the same period. For the past few days, he had taken amoxicillin-clavulanate for presumed sinusitis. Despite this, his symptoms persisted, prompting him to seek further evaluation. His medical history was significant for ulcerative colitis and he had some bloody diarrhea for the past few weeks. Medications included aspirin, mesalamine, multivitamins, folic acid, and herbal supplements including gingko biloba, ginseng, and turmeric-ginger. He never smoked and drank alcohol occasionally. Family history was notable for stroke and myocardial infarction.

Corticosteroids in Acute Lung Injury: The Dilemma Continues.

Acute lung injury (ALI) represents a serious heterogenous pulmonary disorder with high mortality. Despite improved understanding of the pathophysiology, the efficacy of standard therapies such as lung-protective mechanical ventilation, prone positioning and administration of neuromuscular blocking agents is limited. Recent studies have shown some benefits of corticosteroids (CS). Prolonged use of CS can shorten duration of mechanical ventilation, duration of hospitalization or improve oxygenation, probably because of a wide spectrum of potentially desired actions including anti-inflammatory, antioxidant, pulmonary vasodilator and anti-oedematous effects. However, the results from experimental vs. clinical studies as well as among the clinical trials are often controversial, probably due to differences in the designs of the trials. Thus, before the use of CS in ARDS can be definitively confirmed or refused, the additional studies should be carried on to determine the most appropriate dosing, timing and choice of CS and to analyse the potential risks of CS administration in various groups of patients with ARDS.

The Effect of Intravenous Selenium on Oxidative Stress in Critically Ill Patients with Acute Respiratory Distress Syndrome.

OBJECTIVE: To modulate the inflammatory response in respiratory distress syndrome (ARDS) with selenium. BACKGROUND: Selenium replenishes the glutathione peroxidase proteins that are the first line of defense for an oxidative injury to the lungs. METHODS: Forty patients with ARDS were randomized into two groups: the SEL+ group being administered sodium selenite and the SEL- group receiving normal saline for 10 days. Blood samples were taken on Day-0, DAY-7, and Day-14 for assessment of IL-1 beta, IL-6, C-reactive protein, GPx-3, and selenium. Ferric reducing antioxidant power (FRAP) was measured in the bronchial wash fluids. Pearson correlation and repeated measure analysis were performed to examine the effects of selenium on the inflammatory markers. RESULTS: Sodium selenite replenished selenium levels in the SEL+ group. Selenium concentrations were linearly correlated to serum concentrations of GPx3 (R value: 0.631; P < 0.001), and FRAP (R value: -0.785; P < 0.001). Serum concentrations of both IL 1-beta (R value: -0.624; P < 0.001) and IL-6 (R value: -0.642; P < 0.001) were inversely correlated to the serum concentrations of selenium. There was a meaningful difference between two groups in airway resistance and pulmonary compliance changes (P values 0.008 and 0.028, respectively). CONCLUSION: Selenium restored the antioxidant capacity of the lungs, moderated the inflammatory responses, and meaningfully improved the respiratory mechanics. Despite these changes, it had no effect on the overall survival, the duration of mechanical ventilation, and ICU stay. Selenium can be used safely; however, more trials are essential to examine its clinical effectiveness.

Paraquat poisoning: Acute lung injury - a missed diagnosis.

Paraquat is a herbicide of great toxicological importance because it is associated with high mortality rates, mainly due to respiratory failure. We report the case of a 28-year-old man admitted to the casualty department at Ngwelezana Hospital, Empangeni, KwaZulu-Natal, South Africa, with a history of vomiting and abdominal pain after ingestion of ~100 mL of an unknown substance, later identified as paraquat, together with an unknown amount of alcohol, in a suicide attempt. He developed respiratory distress associated with lung parenchymal infiltrates that required ventilatory support and later a spontaneous pneumothorax, and died in the intensive care unit. We discuss the importance of a high index of suspicion of paraquat poisoning in rural areas, where paraquat is readily available as a herbicide on farms, in patients with a similar presentation. We further stress the importance of identifying the classic radiological progression after paraquat poisoning, to help avoid a delay in diagnosis if the culprit substance is not known (as happened in our case). Lastly, we look at the importance of avoiding oxygen supplementation, and early administration of immunosuppressive therapy, to improve outcome.

Current Concepts of ARDS: A Narrative Review.

Acute respiratory distress syndrome (ARDS) is characterized by the acute onset of pulmonary edema of non-cardiogenic origin, along with bilateral pulmonary infiltrates and reduction in respiratory system compliance. The hallmark of the syndrome is refractory hypoxemia. Despite its first description dates back in the late 1970s, a new definition has recently been proposed. However, the definition remains based on clinical characteristic. In the present review, the diagnostic workup and the pathophysiology of the syndrome will be presented. Therapeutic approaches to ARDS, including lung protective ventilation, prone positioning, neuromuscular blockade, inhaled vasodilators, corticosteroids and recruitment manoeuvres will be reviewed. We will underline how a holistic framework of respiratory and hemodynamic support should be provided to patients with ARDS, aiming to ensure adequate gas exchange by promoting lung recruitment while minimizing the risk of ventilator-induced lung injury. To do so, lung recruitability should be considered, as well as the avoidance of lung overstress by monitoring transpulmonary pressure or airway driving pressure. In the most severe cases, neuromuscular blockade, prone positioning, and extra-corporeal life support (alone or in combination) should be taken into account.

Severe hypoxemia: which strategy to choose.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by a noncardiogenic pulmonary edema with bilateral chest X-ray opacities and reduction in lung compliance, and the hallmark of the syndrome is hypoxemia refractory to oxygen therapy. Severe hypoxemia (PaO2/FiO2 < 100 mmHg), which defines severe ARDS, can be found in 20-30 % of the patients and is associated with the highest mortality rate. Although the standard supportive treatment remains mechanical ventilation (noninvasive and invasive), possible adjuvant therapies can be considered. We performed an up-to-date clinical review of the possible available strategies for ARDS patients with severe hypoxemia. MAIN RESULTS: In summary, in moderate-to-severe ARDS or in the presence of other organ failure, noninvasive ventilatory support presents a high risk of failure: in those cases the risk/benefit of delayed mechanical ventilation should be evaluated carefully. Tailoring mechanical ventilation to the individual patient is fundamental to reduce the risk of ventilation-induced lung injury (VILI): it is mandatory to apply a low tidal volume, while the optimal level of positive end-expiratory pressure should be selected after a stratification of the severity of the disease, also taking into account lung recruitability; monitoring transpulmonary pressure or airway driving pressure can help to avoid lung overstress. Targeting oxygenation of 88-92 % and tolerating a moderate level of hypercapnia are a safe choice. Neuromuscular blocking agents (NMBAs) are useful to maintain patient-ventilation synchrony in the first hours; prone positioning improves oxygenation in most cases and promotes a more homogeneous distribution of ventilation, reducing the risk of VILI; both treatments, also in combination, are associated with an improvement in outcome if applied in the acute phase in the most severe cases. The use of extracorporeal membrane oxygenation (ECMO) in severe ARDS is increasing worldwide, but because of a lack of randomized trials is still considered a rescue therapy. CONCLUSION: Severe ARDS patients should receive a holistic framework of respiratory and hemodynamic support aimed to ensure adequate gas exchange while minimizing the risk of VILI, by promoting lung recruitment and setting protective mechanical ventilation. In the most severe cases, NMBAs, prone positioning, and ECMO should be considered.

A case of tension pneumothorax during hyperbaric oxygen therapy in an earthquake survivor with crush injury complicated by ARDS (adult respiratory distress syndrome).

Pneumothorax (PTX) is rarely reported in patients receiving hyperbaric oxygen (HBO2) therapy. Patients with air-trapping lesions in the lungs and those with a history of spontaneous PTX, lung disease, mechanical ventilation or chest trauma are at an increased risk for PTX during HBO2 therapy. A 28-year-old male earthquake survivor was referred to our center for multiple wounds 21 days after being rescued from the debris. He had been intubated and put on mechanical ventilation for three days because of adult respiratory distress syndrome (ARDS). At initial presentation, he was conscious, well-oriented and hemodynamically stable. The initial six HBO2 treatments were uneventful. On the seventh HBO2 treatment, the patient lost consciousness and developed cardiopulmonary arrest near the end of decompression. The HBO2 specialist accompanying the patient inside the chamber immediately initiated CPR. A diagnosis of tension PTX was made. After the patient was removed from the chamber, a chest tube was inserted, which improved the symptoms. Although rare, tension PTX can occur during HBO2 therapy. Early diagnosis and intervention are crucial for saving a patient's life. Increased vigilance is required during treatment of patients with risk factors for PTX.

Etiologies of illness among patients meeting integrated management of adolescent and adult illness district clinician manual criteria for severe infections in northern Tanzania: implications for empiric antimicrobial therapy.

We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.

A case of Clostridium difficile infection complicated by acute respiratory distress syndrome treated with fecal microbiota transplantation.

Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia. Clostridium difficile infection (CDI) is a common nosocomial diarrheal disease. Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI. The use of broad-spectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome. Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI. Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.

[Nutrition and acute respiratory failure]. / Ernährung und Lungenversagen.

Acute respiratory distress syndrome (ARDS) is characterized by the formation of a protein-rich alveolar edema caused by increased permeability of the alveolocapillary membrane. The key clinical feature is refractory arterial hypoxemia, which in severe cases necessitates the application of extracorporeal membrane oxygenation. Besides lung-protective ventilation as a confirmed therapeutic option, supportive therapy is an integral part of ARDS management. In this context, modern and individualized nutritional regimens are of special importance; however, their prognostic impact, especially of immunonutrition, for ARDS patients is controversial. In this review, basic features of nutrition in intensive care medicine and ARDS-specific aspects (e.g., immunonutrition) are presented and discussed.

Acute respiratory distress syndrome: evaluation and management.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition that affects patients admitted in the Intensive Care Units (ICUs) under mechanical ventilation. ARDS is a process of non-hydrostatic pulmonary edema and hypoxemia associated with a variety of conditions, resulting in a direct (e.g., pneumonia) or indirect (e.g., sepsis) lung injury and is associated with a significant morbidity and mortality. A large body of clinical and basic research has focused in ventilatory strategies and novel pharmacological therapies but, nowadays, treatment is mainly supportive. Mechanical ventilation is the hallmark of the management of these patients. In the last decades, the recognition that mechanical ventilation can contribute to harming the lung has changed the goals of this therapy and has driven research to focus in ventilatory strategies that mitigate lung injury. This review emphasizes clinical aspects in the evaluation and management of ARDS in the ICUs and updates the latest advances in these therapies.

Acute respiratory distress syndrome and acute lung injury.

Acute respiratory distress syndrome (ARDS) is a life threatening respiratory failure due to lung injury from a variety of precipitants. Pathologically ARDS is characterised by diffuse alveolar damage, alveolar capillary leakage, and protein rich pulmonary oedema leading to the clinical manifestation of poor lung compliance, severe hypoxaemia, and bilateral infiltrates on chest radiograph. Several aetiological factors associated with the development of ARDS are identified with sepsis, pneumonia, and trauma with multiple transfusions accounting for most cases. Despite the absence of a robust diagnostic definition, extensive epidemiological investigations suggest ARDS remains a significant health burden with substantial morbidity and mortality. Improvements in outcome following ARDS over the past decade are in part due to improved strategies of mechanical ventilation and advanced support of other failing organs. Optimal treatment involves judicious fluid management, protective lung ventilation with low tidal volumes and moderate positive end expiratory pressure, multi-organ support, and treatment where possible of the underlying cause. Moreover, advances in general supportive measures such as appropriate antimicrobial therapy, early enteral nutrition, prophylaxis against venous thromboembolism and gastrointestinal ulceration are likely contributory reasons for the improved outcomes. Although therapies such as corticosteroids, nitric oxide, prostacyclins, exogenous surfactants, ketoconazole and antioxidants have shown promising clinical effects in animal models, these have failed to translate positively in human studies. Most recently, clinical trials with ß2 agonists aiding alveolar fluid clearance and immunonutrition with omega-3 fatty acids have also provided disappointing results. Despite these negative studies, mortality seems to be in decline due to advances in overall patient care. Future directions of research are likely to concentrate on identifying potential biomarkers or genetic markers to facilitate diagnosis, with phenotyping of patients to predict outcome and treatment response. Pharmacotherapies remain experimental and recent advances in the modulation of inflammation and novel cellular based therapies, such as mesenchymal stem cells, may reduce lung injury and facilitate repair.

Life-threatening hypokalaemic paralysis associated with distal renal tubular acidosis.

A 56-year-old woman developed acute respiratory failure requiring mechanical ventilation due to acute hypokalaemic paralysis. There was no gastrointestinal potassium loss nor was she taking diuretics. Additional analyses revealed a normal anion gap metabolic acidosis with a positive urine anion gap. An acid-load test revealed a renal urine acidification defect, leading to the diagnosis of distal renal tubular acidosis. Normalisation of serum potassium level was established with oral bicarbonate supplementation and temporary potassium supplementation.

Acute respiratory distress syndrome after transcatheter arterial chemoembolization of hepatocellular carcinomas.

BACKGROUND: Acute respiratory distress syndrome (ARDS) associated with pulmonary lipiodol embolism is a rare complication of transcatheter arterial chemoembolization (TACE). We performed a survey of ARDS associated with pulmonary lipiodol embolism after TACE. METHODS: A retrospective analysis of the cases of all patients with hepatic tumors who received transcatheter arterial embolization or TACE between January 2006 and December 2006 was performed. The diagnosis of pulmonary lipiodol embolism was confirmed by chest computed tomography (CT). RESULTS: The diagnosis of ARDS associated with pulmonary lipiodol embolism was confirmed in 4 patients. All had large (> or =5 cm) and hypervascular tumors. There was no evidence of hepatocellular carcinoma arteriovenous shunting in any of our patients as determined by angiography and multidetector CT. The volumes of lipiodol infused in the 4 patients were 50, 20, 30, and 20 mL. Only 2 patients received injections of carcinostatic agents. The onset of respiratory symptoms occurred between 1 hour and 4 days after TACE. Respiratory symptoms consisted of dyspnea and tachypnea. Chest CT scans revealed linear high-density shadows, suggestive of lipiodol retention in both lungs of all patients. CONCLUSION: Pulmonary lipiodol embolism after TACE can occur within a short time frame. Whether or not there is intrahepatic arteriovenous shunting detected by multidetector CT and angiography, clinicians should avoid high doses of iodized oil and carcinostatic agents. We suggest that CT should be used for the diagnosis of pulmonary lipiodol embolism.

[Case of drug-induced pneumonia due to Saiko-karyuukotsu-boreitou].

We present a case of acute respiratory distress syndrome (ARDS) caused by allergic reactions to a herbal drug Saiko-karyuukotu-boreitou. A 57-year-old woman was admitted with a chief complaint of dry cough and dyspnea. She had been treated with Saiko-karyuukotsu-boreitou for postoperative pain and insomnia. Chest radiographs on admission showed diffuse infiltration shadows in both lungs. Chest CT scan showed diffuse ground glass opacities, consolidation and air bronchogram. Drug stimulation test was positive for Saiko-karyuukotu-boreitou. Based on the above findings, we diagnosed this case as Saiko-karyuukotu-boreitou-induced pneumonia. The patient recovered after discontinuation of Saiko-karyuukotu-boreitou. This is the fourth reported case of pneumonia induced by Saiko-karyuukotu-boreitou. We recommend careful observation when this medicine is prescribed.

[Vegetable oil-induced acute respiratory distress syndrome (ARDS) in near drowning: evaluation based on extravascular lung water index].

Lipoid pneumonia usually presents after chronic recurrent ingestion of oily substances or accidental aspiration during "fire-eating" demonstrations. Massive exposure by near drowning extremely rare and potentially fatal. We present here a case of survival after total immersion in oil in her workplace. A 66-year-old woman who nearly drowned in a vat of vegetable oil was admitted as an emergency case with severe hypoxia after rescue. Chest computed tomography (CT) findings showed bilateral ground-glass opacity, consolidation, and the case fulfilled the criteria for acute respiratory distress syndrome (ARDS). Bronchoscopy and bronchoalveolar lavage performed on admission indicated oil droplets and marked neutrophilia (67%), which made us diagnose ARDS induced by lipoid pneumonia. We commenced treatment with pulsed steroids and strictly managed fluid balance under mechanical ventilation. Despite immediate improvement in oxygenation, the value of extravascular lung water index (EVLWI) measured by the PiCCO system consistently remained over 30 ml/Kg through her clinical course. We concluded that lipoid pneumonia is characterized by prolonged elevatation of pulmonary vascular permeability.