Pneumonia-induced Acute Respiratory Distress Syndrome Research Articles

Axillary vein as an alternative venous access site for VV-ECMO cannulation: a case report

BackgroundUltrasound-guided percutaneous axillary vein cannulation can reduce cannulation failure and mechanical complications, is as safe and effective as internal jugular vein cannulation, and is superior to subclavian vein cannulation using landmark technique. As far, reports of venovenous extracorporeal membrane oxygenation (VV-ECMO) with percutaneous axillary vein cannulation are rare.Case presentationA 64-year-old man presenting with dyspnea and chest tightness after aspirating sewage was admitted to the emergency department. Computed tomography (CT) showed diffuse exudation of both lungs and arterial blood gas analysis showed an oxygenation index of 86. He was diagnosed with aspiration pneumonia-induced acute respiratory distress syndrome (ARDS) and intubated for deteriorated oxygenation. Despite the combination therapy of protective mechanical ventilation and prone position, the patient’s oxygenation deteriorated further, accompanied with multiple organ dysfunction syndrome, which indicated the requirement of support with VV-ECMO. However, vascular ultrasound detected multiple thrombus within bilateral internal jugular veins. As an alternative, right axillary vein was chosen as the access site of return cannula. Subsequently, femoral-axillary VV-ECMO was successfully implemented under the ultrasound guidance, and the patient’s oxygenation was significantly improved. Unfortunately, the patient died of hyperkalemia-induced ventricular fibrillation after 36 h of VV-ECMO running. Despite the poor prognosis, the blood flow during ECMO run was stable, and we observed no bleeding complication, vascular injury, or venous return disorder.ConclusionsAxillary vein is a feasible alternative access site of return cannula for VV-ECMO if internal jugular vein access were unavailable.

COVID-19 induced ARDS: immunopathology and therapeutics

The coronavirus disease-2019 (COVID-19) pandemic is a significant threat in the modern era. Clinical studies show that the most common symptom of severe COVID-19 is viral pneumonia-induced acute respiratory distress syndrome (ARDS). The underlying mechanisms by which severe respiratory disease syndrome-coronavirus-2 (SARS-CoV-2) results in ARDS and how certain host factors confer an increased risk of developing severe disease remain unknown. Therefore, identifying the distinctive features of this severe and fatal disease and the therapeutic approaches to COVID-19-induced ARDS remains an immediate need to serve as a basis for best practice models of standardized ARDS treatment. This review article aims to comprehensively discuss the immunopathology of ARDS and provides an overview of the precise role of both the innate and adaptive immune system, with emphasis on the current treatment strategies being tested in the COVID-19-induced ARDS patients. This knowledge will supposedly help in revealing further mechanistic insights into understanding COVID-19-induced ARDS.

Knockdown of lncRNA-ASLNC12002 alleviates epithelial–mesenchymal transition of type II alveolar epithelial cells in sepsis-induced acute respiratory distress syndrome

Patients with sepsis-induced acute respiratory distress syndrome (ARDS) have higher mortality and poor prognosis than pneumonia-induced ARDS. Pulmonary fibrosis is an irreversible accumulation of connective tissue in the interstitium of the lung and closely associated with the epithelial–mesenchymal transition (EMT) of type II alveolar epithelial cells (AECIIs). Therefore, it is undoubtedly worth studying whether the EMT of AECIIs in sepsis-induced ARDS patients is different from that in patients with pneumonia-induced ARDS in the regulatory mechanism. Here, we will report for the first time that an lncRNA-ASLNC12002 is highly expressed in AECIIs of patients with sepsis-induced pneumonia and promotes EMT in AECIIs. The research results showed that the expression of ASLNC12002 in AECIIs derived from patients with sepsis-induced ARDS is significantly higher than that in normal people and pneumonia-induced ARDS patients. Mechanism research showed that ASLNC12002 can cause the inactivation of the anti-EMT pathway NR2F2/miR128-3p/Snail1 by acting as the sponge of miR128-3p. Functional experiments showed that targeted silencing of ASLNC12002 could effectively inhibit EMT progression in AECIIs of patients with sepsis-induced pneumonia by restoring NR2F2/miR128-3p/Snail1 pathway. In a word, our study shows for the first time that the inactivation of NR2F2/miR128-3p/Snail1 pathway caused by the enhanced expression of ASLNC12002 is the direct reason why AECIIs in sepsis-induced ARDS patients are prone to get EMT progress. ASLNC12002 has the potential to become a biological target for the prevention and treatment of pulmonary fibrosis in patients with sepsis-induced ARDS. At the same time, the expectation that ASLNC12002 and its related products may be used as clinical markers for the evaluation of early pulmonary fibrosis in ARDS patients should not be ignored.

Loss of endothelial CFTR drives barrier failure and edema formation in lung infection and can be targeted by CFTR potentiation

Pneumonia is the most common cause of the acute respiratory distress syndrome (ARDS). Here, we identified loss of endothelial cystic fibrosis transmembrane conductance regulator (CFTR) as an important pathomechanism leading to lung barrier failure in pneumonia-induced ARDS. CFTR was down-regulated after Streptococcus pneumoniae infection ex vivo or in vivo in human or murine lung tissue, respectively. Analysis of isolated perfused rat lungs revealed that CFTR inhibition increased endothelial permeability in parallel with intracellular chloride ion and calcium ion concentrations ([Cl-]i and [Ca2+]i). Inhibition of the chloride ion-sensitive with-no-lysine kinase 1 (WNK1) protein with tyrphostin 47 or WNK463 replicated the effect of CFTR inhibition on endothelial permeability and endothelial [Ca2+]i, whereas WNK1 activation by temozolomide attenuated it. Endothelial [Ca2+]i transients and permeability in response to inhibition of either CFTR or WNK1 were prevented by inhibition of the cation channel transient receptor potential vanilloid 4 (TRPV4). Mice deficient in Trpv4 (Trpv4-/-) developed less lung edema and protein leak than their wild-type littermates after infection with S. pneumoniae. The CFTR potentiator ivacaftor prevented lung CFTR loss, edema, and protein leak after S. pneumoniae infection in wild-type mice. In conclusion, lung infection caused loss of CFTR that promoted lung edema formation through intracellular chloride ion accumulation, inhibition of WNK1, and subsequent disinhibition of TRPV4, resulting in endothelial calcium ion influx and vascular barrier failure. Ivacaftor prevented CFTR loss in the lungs of mice with pneumonia and may, therefore, represent a possible therapeutic strategy in people suffering from ARDS due to severe pneumonia.

Loss of Endothelial CFTR Drives Barrier Failure and Edema Formation in Lung Infection and Can Be Targeted by CFTR Potentiation

Pneumonia is the most common cause of the acute respiratory distress syndrome (ARDS), a potentially fatal lung disease characterized by hyperinflammation and endothelial barrier failure. Infectious and inflammatory stimuli can cause rapid downregulation of cystic fibrosis transmembrane conductance regulator (CFTR), and inhibition of CFTR has been proposed to increase lung microvascular endothelial permeability in vitro. Here, we identify loss of lung microvascular endothelial CFTR as important pathomechanism in lung barrier failure in pneumonia‐induced ARDS, delineate the molecular signaling pathway underlying this effect and identify CFTR potentiation as novel therapeutic strategy in ARDS.CFTR was downregulated in endothelial cells following Streptococcus pneumoniae(S.pn.) infection in human and murine lung tissue. Isolated perfused lungs revealed that CFTR inhibition increased endothelial permeability in parallel with intracellular Cl‐ and Ca2+concentrations ([Cl‐]i, [Ca2+]i). Inhibition of the Cl‐ sensitive with‐no‐lysine kinase 1 (WNK1) replicated the effect of CFTR inhibition on endothelial permeability and endothelial [Ca2+]i while WNK1 activation attenuated it. Endothelial [Ca2+]i transients and permeability in response to inhibition of either CFTR or WNK1 were prevented by inhibition of the cation channel transient receptor potential vanilloid 4 (TRPV4). Mice deficient in Trpv4 (Trpv4‐/‐) developed less lung edema and protein leak than their wild‐type littermates following infection with S. pn. Conversely, lungs of heterozygous Wnk1‐deficient mice (Wnk1+/‑) showed spontaneous leak. The CFTR potentiator ivacaftor prevented CFTR loss and reduced endothelial leak in response to pneumolysin (PLY), a key S.pn. virulence factor, or plasma from COVID‐19 patients in vitro, and prevented lung edema and protein leak after S. pn.infection in vivo.Lung infection causes rapid loss of CFTR that promotes lung edema formation through intracellular Cl‐accumulation, inhibition of WNK1 and subsequent disinhibition of TRPV4, resulting in endothelial Ca2+ influx and vascular barrier failure. Ivacaftor prevents CFTR loss and may thus present a promising therapeutic strategy in ARDS due to severe pneumonia including COVID‐19.

A combination of the APACHE II score, neutrophil/lymphocyte ratio, and expired tidal volume could predict non-invasive ventilation failure in pneumonia-induced mild to moderate acute respiratory distress syndrome patients.

BackgroundNoninvasive ventilation (NIV) failure rate is relatively high in patients with acute respiratory distress syndrome (ARDS). Currently the data regarding prediction of NIV failure of pneumonia-induced mild to ARDS patients were scarce.MethodsA total of 364 patients (from January 2016 to December 2020) diagnosed with hypoxemic respiratory failure and managed with NIV were initially included and finally 131 pneumonia-induced mild to moderate ARDS patients were enrolled in this study. Electronic medical records were reviewed to determine whether NIV succeeded or failed for each patient. The relationship between the Acute Physiology And Chronic Health Evaluation II (APACHE II) score , neutrophil/lymphocyte ratio (NLR), expired tidal volume (Vte) and NIV failure were specifically analyzed. Multivariate logistic regression analyses were conducted to identify the independent factors of NIV failure. Receiver-operating characteristic curves were used to assess the efficacy of the variables in predicting NIV failure. Kaplan-Meier curves for 28-day survival were used to compare the mortality rates of different groups.ResultsOf the patients, 64 (48.9%) experienced NIV failure, APACHE II score [odds ratio (OR) =0.77; P=0.002], NLR (OR =0.838; P=0.046), and Vte (OR =0.343; P=0.009) were independent factors for predicting NIV failure. A combined value comprising the APACHE II score, NLR, and Vte had better efficacy at predicting NIV failure [area under the curve (AUC) =0.9; 95% confidence interval (CI): 0.845–0.955] than the APACHE II score (AUC =0.818; 95% CI: 0.745–0.891), NLR (AUC =0.839; 95% CI: 0.765–0.913), or Vte (AUC =0.805; 95% CI: 0.729–0.881) alone. The cumulative survival probability within 28 days was lower in patients with a combined value >59.17 (P<0.001 by the log-rank test), an APACHE II score >16.5 (P<0.001 by the log-rank test), an NLR >7.22 (P<0.001 by the log-rank test), and a Vte >8.96 mL/kg (P<0.001 by log-rank test).ConclusionsA combined value comprising an APACHE II score >16.5, a NLR >7.22, and a Vte >8.96 mL/kg may be a useful surrogate for predicting NIV failure among pneumonia-induced ARDS patients, and patients with a combined value >59.17 should be cautiously monitored during NIV. A further study with a larger sample size is warranted.

Advancing Pulmonary Rehabilitation Approach in Improving Well-being in a Long COVID-19 Syndrome Case

Being a highly contagious disease, Coronavirus Disease-2019 (COVID-19) has shown its impact throughout the world. Clinical manifestations are seen primarily involving the respiratory system. Fever, cough, fatigue, and breathlessness are the commonly seen symptoms. Several cases of COVID-19 manifest as viral pneumonia-induced Acute Respiratory Distress Syndrome (ARDS). COVID19 symptoms appear not only during the course of the illness but also as its after effects. Long COVID-19 is said to be multisystem syndrome, categorised as postacute or chronic depending upon the time frame. It is characterized by the presence of symptoms beyond four weeks of the actual disease. Change in structural components in the lung leads to having a functional consequence on the body, affecting the cognitive, psychosocial, mental and physical well-being of the patients. Studies have shown alveolar damage same as ARDS. The most common pulmonary sequences seen are dyspnoea, cough (dry/with expectoration) and decreased diffusion capacity leading to reduced endurance. The present case report was of a 45-year-old nurse, who presented with the symptoms of postacute long COVID-19. Her previous scan of thorax showed a severity score of 11/25 after being tested COVID-19 positive. In view of the presenting complaints, a tailor-made pulmonary rehabilitation program was administered which showed great improvement in overall health condition. This case had been reported to document the effects of post COVID rehabilitation program on aspects such as functional capacity, quality of life, anxiety and depression using novel measures such as Incremental Shuttle Walk Test (ISWT), World Health Organisation Quality of Life-Brief Version (WHOQOL-BREF), and Depression, Anxiety and Stress Scale - 21 Items (DASS-21). Rehabilitation has been proven to be effective and safe in improving the exercise performance, quality of life affected due to COVID-19 and psychological function of the patients.

Clinical phenotypes from fatal cases of acute respiratory distress syndrome caused by pneumonia

There have been no report of objective clinical characteristics or prognostic factors that predict fatal outcome of acute respiratory distress syndrome (ARDS) since the Berlin definition was published. The aim of this study is to identify clinically available predictors that distinguish between two phenotypes of fatal ARDS due to pneumonia. In total, 104 cases of Japanese patients with pneumonia-induced ARDS were extracted from our prospectively collected database. Fatal cases were divided into early (< 7 days after diagnosis) and late (≥ 7 days) death groups, and clinical variables and prognostic factors were statistically evaluated. Of the 50 patients who died within 180 days, 18 (36%) and 32 (64%) were in the early (median 2 days, IQR [1, 5]) and late (median 16 days, IQR [13, 29]) death groups, respectively. According to multivariate regression analyses, the APACHE II score (HR 1.25, 95%CI 1.12–1.39, p < 0.001) and the disseminated intravascular coagulation score (HR 1.54, 95%CI 1.15–2.04, p = 0.003) were independent prognostic factors for early death. In contrast, late death was associated with high-resolution computed tomography (HRCT) score indicating early fibroproliferation (HR 1.28, 95%CI 1.13–1.42, p < 0.001) as well as the disseminated intravascular coagulation score (HR 1.24, 95%CI 1.01–1.52, p = 0.039). The extent of fibroproliferation on HRCT, and the APACHE II scores along with coagulation abnormalities, should be considered for use in predictive enrichment and personalized medicine for patients with ARDS due to pneumonia.

Neutrophil Extracellular Traps Augmented Alveolar Macrophage Pyroptosis via AIM2 Inflammasome Activation in LPS-Induced ALI/ARDS.

BackgroundUncontrollable inflammation is a critical feature of gram-negative bacterial pneumonia-induced acute respiratory distress syndrome (ARDS). Both neutrophils and alveolar macrophages participate in inflammation, but how their interaction augments inflammation and triggers ARDS is unclear. The authors hypothesize that neutrophil extracellular traps (NETs), which are formed during neutrophil NETosis, partly cause alveolar macrophage pyroptosis and worsen the severity of ARDS.MethodsThe authors first analysed whether NETs and caspase-1 are involved in clinical cases of ARDS. Then, the authors employed a lipopolysaccharide (LPS)-induced ARDS model to investigate whether targeting NETs or alveolar macrophages is protective. The AIM2 sensor can bind to DNA to promote AIM2 inflammasome activation, so the authors studied whether degradation of NET DNA or silencing of the AIM2 gene could protect alveolar macrophages from pyroptosis in vitro.ResultsAnalysis of aspirate supernatants from ARDS patients showed that NET and caspase-1 levels were correlated with the severity of ARDS and that the levels of NETs and caspase-1 were higher in nonsurvivors than in survivors. In vivo, the NET level and proportion of pyroptotic alveolar macrophages in bronchoalveolar lavage fluid (BALF) were obviously higher in LPS-challenged mice than in control mice 24 h after injury. Administration of DNase I (a NET DNA-degrading agent) and BB-Cl-amidine (a NET formation inhibitor) alleviated alveolar macrophage pyroptosis, and Ac-YVAD-cmk (a pyroptosis inhibitor) attenuated NET levels in BALF and neutrophil infiltration in alveoli. All treatments markedly attenuated the severity of ARDS. Notably, LPS causes NETs to induce alveolar macrophage pyroptosis, and degradation of NET DNA or silencing of the AIM2 gene protected against alveolar macrophage pyroptosis.ConclusionThese findings shed light on the proinflammatory role of NETs in mediating the neutrophil–alveolar macrophage interaction, which influences the progression of ARDS.

A Systematic Review of Coronavirus Disease 2019 with Respiratory Distress Syndrome in Adult: Focus on Risk Factors, Mechanism, Diagnosis, and Treatment

&lt;p&gt;&lt;strong&gt;Context: &lt;/strong&gt;Coronavirus disease 2019 (COVID-19) is a newly discovered disease, caused by SARS-CoV-2 and currently has become a pandemic. Acute respiratory distress syndrome (ARDS) is the most common complication in COVID-19. There were numerous conflicting results among articles related to it. The aim of this study is to ascertain the most compelling evidence about ARDS in COVID-19.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Evidence Acquisition: &lt;/strong&gt;This systematic review was registered in PROSPERO (CRD42020180379). A systematic search was conducted in PubMed, PubMed central, and Google Scholar on April 16, 2020. Two reviewers independently searched and selected the articles. The risk of bias was evaluated using the Newcastle-Ottawa Quality assessment tool.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 1,647 articles were screened, 9 articles were included. Patients were classified as having various degrees of ARDS, the diagnosis of COVID-19 was confirmed by PCR nasopharyngeal swab. Risk factors of ARDS in COVID-19 reported were older age, male gender, and pre-existing medical conditions. Cytokine storm was thought to play a role in the mechanism of ARDS. The main treatment for COVID-19 was supportive and symptomatic. To date, there is no antiviral treatment recommended for COVID-19 and the given treatment for ARDS in COVID-19 was similar to other pneumonia-induced ARDS. No additional therapy specific for ARDS in COVID-19 has been proposed.&lt;/p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our synthesis of the literature showed that there was no good evidence in the mechanism and treatment of ARDS. Further translation research in the mechanism of ARDS and continuing with clinical trials evaluating drug efficacy for ARDS in COVID-19 is needed.

Clinical Course and Outcome of COVID-19 Acute Respiratory Distress Syndrome: Data From a National Repository.

Mortality attributable to coronavirus disease-19 (COVID-19) 2 infection occurs mainly through the development of viral pneumonia-induced acute respiratory distress syndrome (ARDS). The objective of the study is to delineate the clinical profile, predictors of disease progression, and 30-day mortality from ARDS using the Veterans Affairs Corporate Data Warehouse. Analysis of a historical cohort of 7,816 hospitalized patients with confirmed COVID-19 infection between January 1, 2020, and August 1, 2020. Main outcomes were progression to ARDS and 30-day mortality from ARDS, respectively. The cohort was comprised predominantly of men (94.5%) with a median age of 69 years (interquartile range [IQR] 60-74 years). 2,184 (28%) were admitted to the intensive care unit and 643 (29.4%) were diagnosed with ARDS. The median Charlson Index was 3 (IQR 1-5). Independent predictors of progression to ARDS were body mass index (BMI) ≥40 kg/m2, diabetes, lymphocyte counts <700 × 109/L, LDH >450 U/L, ferritin >862 ng/ml, C-reactive protein >11 mg/dL, and D-dimer >1.5 ug/ml. In contrast, the use of an anticoagulant lowered the risk of developing ARDS (OR 0.66 [95% CI 0.49-0.89]. Crude 30-day mortality rate from ARDS was 41% (95% CI 38%-45%). Risk of death from ARDS was significantly higher in those who developed acute renal failure and septic shock. Use of an anticoagulant was associated with 2-fold reduction in mortality. Survival benefit was observed in patients who received corticosteroids and/or remdesivir but there was no advantage of combination therapy over either agent alone. Among those hospitalized for COVID-19, nearly 1 in 10 progressed to ARDS. Septic shock, and acute renal failure are the leading causes of death in these patients. Treatment with either remdesivir and corticosteroids reduced the risk of mortality from ARDS. All hospitalized patients with COVID-19 should be placed at a minimum on prophylactic doses of anticoagulation.

Immunological response to COVID-19 and its role as a predisposing factor in invasive aspergillosis.

The world is involved with a pandemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2. The clinical manifestations of reported COVID-19-associated pulmonary impairments range from asymptomatic infections to a pneumonia-induced acute respiratory distress syndrome that requires mechanical ventilation. Fungal superinfections complicating the clinical course remain underexplored. Angiotensin-converting enzyme 2, the receptor for COVID-19 that is mainly expressed in airway epithelia and lung parenchyma, is considered an important regulator of innate immunity. With regard to the viral-cell interaction, imbalanced immune regulation between protective and altered responses caused by the exacerbation of inflammatory responses should be considered a major contributor to secondary pulmonary aspergillosis. In addition, the complex inherited factors, age-related changes, and lifestyle may also affect immune responses. The complication and persistence of invasive aspergillosis have been well described in patients with severe influenza or COVID-19. However, there is a scarcity of information about the immunological mechanisms predisposing patients with COVID-19 to fungal co-infections. Therefore, this study was conducted to investigate the aforementioned domain.

The overlooked chamber in coronavirus disease 2019.

Coronavirus disease 2019 (COVID‐19) causes a pandemic around the globe. Debilitating and even deadly complications have occurred to the millions. A recent study reported 31% of right ventricular dilation in the hospitalized COVID‐19 patients, which is significantly associated with the mortality. Therefore, we sought to search for the lines of evidence in the literature that COVID‐19 may contribute to right heart dysfunction. The relevant literature and data from PubMed, Embase, Cochrane Library databases, and Web of Science were searched using the MeSH terms including ‘COVID‐19’, ‘SARS‐CoV‐2’, ‘novel coronavirus pneumonia’, ‘novel coronavirus’, ‘right heart failure’, ‘right heart dysfunction’, ‘pulmonary hypertension’, ‘pulmonary embolism’, and various combinations. The collected literature and data were sorted and summarized. Literature reports that angiotensin‐converting enzyme 2 (ACE2) is the host receptor mediating the cell entry of severe acute respiratory syndrome coronavirus 2. Clinical and experimental evidence shows that loss of function of ACE2 aggravates pulmonary hypertension and gain of function of ACE2 exerts protection on cardiopulmonary circulation. Moreover, the patients with COVID‐19 are more susceptible to pulmonary embolism and severe pneumonia‐induced acute respiratory distress syndrome. Therefore, COVID‐19 may cause right heart dysfunction by inducing pulmonary hypertension, pulmonary embolism, and acute respiratory distress syndrome. Particular attention should be paid to the function of the right heart, the overlooked chamber in COVID‐19. Blood gas analysis, laboratory test of cardiac injury markers, physical examination, and echocardiography should be performed to identify right heart failure as early as possible. Once the right heart failure is confirmed, the therapeutic modalities following the guidelines of European Society of Cardiology should be employed to reduce mortality.

Pathogenesis of COVID-19-induced ARDS: implications for an ageing population

The coronavirus disease 2019 (COVID-19) pandemic has elicited a swift response by the scientific community to elucidate the pathogenesis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced lung injury and develop effective therapeutics. Clinical data indicate that severe COVID-19 most commonly manifests as viral pneumonia-induced acute respiratory distress syndrome (ARDS), a clinical entity mechanistically understood best in the context of influenza A virus-induced pneumonia. Similar to influenza, advanced age has emerged as the leading host risk factor for developing severe COVID-19. In this review we connect the current understanding of the SARS-CoV-2 replication cycle and host response to the clinical presentation of COVID-19, borrowing concepts from influenza A virus-induced ARDS pathogenesis and discussing how these ideas inform our evolving understanding of COVID-19-induced ARDS. We also consider important differences between COVID-19 and influenza, mainly the protean clinical presentation and associated lymphopenia of COVID-19, the contrasting role of interferon-γ in mediating the host immune response to these viruses, and the tropism for vascular endothelial cells of SARS-CoV-2, commenting on the potential limitations of influenza as a model for COVID-19. Finally, we explore hallmarks of ageing that could explain the association between advanced age and susceptibility to severe COVID-19.

Analysis of pulmonary vascular injury and repair during Pseudomonas aeruginosa infection-induced pneumonia and acute respiratory distress syndrome.

Herein we describe lung vascular injury and repair using a rodent model of Pseudomonas aeruginosa pneumonia-induced acute respiratory distress syndrome (ARDS) during: 1) the exudative phase (48-hour survivors) and 2) the reparative/fibro-proliferative phase (1-week survivors). Pneumonia was induced by intratracheal instillation of P. aeruginosa strain PA103, and lung morphology and pulmonary vascular function were determined subsequently. Pulmonary vascular function was assessed in mechanically ventilated animals in vivo (air dead space, PaO2, and lung mechanics) and lung permeability was determined in isolated perfused lungs ex vivo (vascular filtration coefficient and extravascular lung water). At 48 hours post infection, histological analyses demonstrated capillary endothelial disruption, diffuse alveolar damage, perivascular cuffs, and neutrophil influx into lung parenchyma. Infected animals displayed clinical hallmarks of ARDS, including increased vascular permeability, increased dead space, impaired gas exchange, and decreased lung compliance. Overall, the animal infection model recapitulated the morphological and functional changes typically observed in lungs from patients during the exudative phase of ARDS. At 1 week post infection, there was lung histological and pulmonary vascular functional evidence of repair when compared with 48 hours post infection; however, some parameters were still impaired when compared with uninfected controls. Importantly, lungs displayed increased fibrosis and cellular hyperplasia reminiscent of lungs from patients during the fibro-proliferative phase of ARDS. Control, sham inoculated animals showed normal lung histology and function. These data represent the first comprehensive assessment of lung pathophysiology during the exudative and reparative/fibro-proliferative phases of P. aeruginosa pneumonia-induced ARDS, and position this pre-clinical model for use in interventional studies aimed at advancing clinical care.

Tuberculous pneumonia-induced severe ARDS complicated with DIC in a female child: a case of successful treatment

BackgroundTuberculous (TB) pneumonia can induce acute respiratory distress syndrome (ARDS). Although TB pneumonia is one of the causes of disease and death among children worldwide, the literature on TB pneumonia-induced ARDS is limited. We report herein on the successful treatment of a two-year-old female child with TB pneumonia-induced severe ARDS complicated with disseminated intravascular coagulation (DIC).Case presentationA two-year-old Vietnamese female child with sustained fever and cough for 20 days was transferred to our hospital. She had severe dyspnea and a chest X-ray showed bilateral infiltration without findings of heart failure. After tracheal intubation, her oxygenation index (OI) and PaO2/FiO2 (PF) ratio were 29 and 60 mmHg, respectively. Mycobacterium tuberculosis was detected by real-time polymerase chain reaction (rPCR) assay of tracheal lavage fluid. She was diagnosed as having severe ARDS that developed from TB pneumonia. Anti-tuberculous therapy and cardiopulmonary support were started. However, her respiratory condition deteriorated despite treatment with high-frequency oscillating ventilation (HFO), vasopressor support, and 1 g/kg of immunoglobulin. On the third day after admission, her International Society on Thrombosis and Hemostasis DIC score had increased to 5. Recombinant human soluble thrombomodulin (rTM) was administered to treat the DIC. After the administration of rTM was completed, OI gradually decreased, after which the mechanical ventilation mode was changed from HFO to synchronized intermittent mandatory ventilation. The DIC score also gradually decreased. Plasma levels of soluble receptor for advanced glycan end products (sRAGE) and high mobility group box 1 (HMGB-1), which are reported to be associated with ARDS severity, also decreased. In addition, inflammatory biomarkers, including interferon-gamma (IFN-γ) and interleukin-6 (IL-6), decreased after the administration of rTM. Although severe ARDS (P/F ratio ≦ 100 mmHg) continued for 19 days, the patient’s OI and P/F ratio improved gradually, and she was extubated on the 27th day after admission. The severe ARDS with DIC was successfully treated, and she was discharged from hospital on day 33 post-admission.ConclusionsWe successfully treated a female child suffering from TB pneumonia-induced severe ARDS complicated with DIC using multimodal interventions. (338/350).

High-frequency percussive ventilation in severe acute respiratory distress syndrome: A single center experience

Background:Few studies have investigated high-frequency percussive ventilation (HFPV) in adult patients with acute respiratory distress syndrome (ARDS).Materials and Methods:We retrospectively analyzed data from critically ill-patients with moderate and severe ARDS who received HFPV. Ventilation and oxygenation were governed according to a predefined protocol. HFPV was continued until patients could be switched to conventional ventilation.Results:A total of 42 patients (20 with pneumonia-related ARDS and 22 non-septic ARDS cases) were evaluable. Baseline demographic characteristics, severity of illness, lung injury score; pH and respiratory variables were comparable between pneumonia and non-sepsis-related ARDS. Within 24 h, HFPV restored normal pH and PaCO2 and considerably improved oxygenation. Oxygenation improved more in non-septic than in pneumonia-related ARDS. Patients with pneumonia-induced ARDS also remained longer HFPV-dependent (7.0 vs. 4.9 days; P < 0.05). Mortality at 30 days was significantly higher in pneumonia-related than in non-sepsis-related ARDS (50% vs. 18%; P = 0.01).Conclusions:HFPV caused rapid and sustained improvement of oxygenation and ventilation in patients with moderate to severe ARDS. Less improved oxygenation, longer ventilator dependency and worse survival were observed in pneumonia-related ARDS.

Inhaled Ribavirin Therapy in Adult Respiratory Syncytial Virus-Induced Acute Respiratory Distress Syndrome

Respiratory syncytial virus (RSV) infection-induced acute respiratory distress syndrome (ARDS) in previously healthy adults is rare, but the overall mortality rate is 40%-60%. Inhaled ribavirin is approved for the treatment of hospitalized infants and young children with severe lower respiratory tract infections due to RSV. We present the case of an adult female with RSV pneumonia-induced ARDS who was successfully treated with inhaled ribavirin and whose pulmonary function was restored to near normal. The role of inhaled ribavirin in adults is controversial, but it might have a therapeutic potential for severe RSV infection-induced ARDS in adults.

Tratamiento con ribavirina inhalada en el síndrome de dificultad respiratoria aguda inducida por virus respiratorio sincitial en el adulto

Respiratory syncytial virus (RSV) infection-induced acute respiratory distress syndrome (ARDS) in previously healthy adults is rare, but the overall mortality rate is 40-60%. Inhaled ribavirin is approved for the treatment of hospitalized infants and young children with severe lower respiratory tract infections due to RSV. We present the case of an adult female with RSV pneumonia-induced ARDS who was successfully treated with inhaled ribavirin and whose pulmonary function was restored to near normal. The role of inhaled ribavirin in adults is controversial, but it might have a therapeutic potential for severe RSV infection-induced ARDS in adults.