Pulmonary Alveolar Proteinosis in a Patient with Severe Flea-Borne Typhus

Elevated BALF concentrations of α- and β-defensins in patients with pulmonary alveolar proteinosis

Lung transplantation for coronavirus disease 2019 (COVID-19): The who, what, where, when, and why

Veno-Pulmonary Arterial Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Distress Syndrome: Should We Consider Mechanical Support of the Pulmonary Circulation From the Outset?

Objective To explore the changes and significance of respiratory mechanics parameters and pulmonary arterial pressure (PAP) of prenatal stage neonates with pulmonary acute respiratory distress syndrome (ARDSp) or extrapulmonary acute respiratory distress syndrome (ARDSexp). Methods From May 2015 to August 2017, a total of 78 prenatal stage neonates with acute respiratory distress syndrome (ARDS) who were admitted to department of Neonatology of the Affiliated Yancheng Hospital of Southeast University Medical College, were chosen as research subjects. According to different causes of ARDS, 41 neonates with ARDSp were including into ARDSp group and 37 neonates with ARDSexp were including into ARDSexp group. And from department of Obstetrics in same hospital during the same period, a total of 40 healthy neonates with same age were included into control group. The severity of 78 ARDS neonates were determined as mild, moderate and severe according to oxygenation index (OI). The independent-samples t test, variance analysis and chi-square test were used to compare the following measurement data or numeration data. ①Comparasion of clinical data, OI and respiratory mechanics parameters between ARDSp group and ARDSexp group; PAP values of different severity degrees of ARDS neonates in each group or between two groups. ②PAP values of ARDSp and ARDSexp groups at 0, 24, 48, 72, 96 h after breath support, and pre-extubation time points, also PAP values of control group at corresponding hourly ages. Pearson correlation analysis was used to analyze the correlation between OI and PAP of 78 neonates with ARDS. This study met the requirements of World Medical Association Declaration of Helsinki revised in 2013. Results ①Perinatal stage neonates′gestational age, birth weight, usage rate of pulmonary surfactant (PS), incidence rate of persistent pulmonary hypertension of newborn (PPHN) and mortality rate of ARDSexp group [(37.5±1.7) gestational weeks, (2 548±465) g, 13.5%, 2.7%, 2.7%] were all lower than those of ADRSp group [(38.9±1.7) gestational weeks, (3 188±513) g, 78.0%, 24.4%, 19.5%], while the success rate of continuous positive airway pressure (CPAP) of ARDSexp group (13.5%) was higher than that of ARDSp group (0), and all the differences were statistically significant (t=3.632, P<0.001; t=5.750, P<0.001; χ2=32.491, P<0.001; χ2=7.552, P=0.006; χ2=5.384, P=0.020; χ2=5.920, P=0.015). ②A total of 73 ARDS neonates accepted invasive mechanical ventilation in this study, and at time point of 24 h, the OI, mean airway pressure (MAP) and airway resistance (Raw) of ARDSexp group [(14.8±4.3), (10.4±2.9) cmH2O, (83.9±18.3) cmH2O/(L·s)] (1 cmH2O=0.098 kPa) were all lower than those of ARDSp group [(18.8±3.2), (15.5±2.4) cmH2O, (115.8±30.7) cmH2O/(L·s)], while compliance of the respiratory system (Crs) of ARDSexp group [(0.39±0.09) mL/(cmH2O·kg)] was higher than that of ARDSp group [(0.26±0.05) mL/(cmH2O·kg)], and all the differences were statistically significant (t=4.561, 8.754, 5.537, 7.713; all P<0.001). ③After 24 h of respiratory support, PAP values of moderate or severe ARDS neonates in ARDSexp group [(54.7±5.9) mmHg, (64.2±4.9) mmHg] (1 mmHg=0.133 kPa) were lower than those in ARDSp group [(62.5±5.4) mmHg, (68.0±6.5) mmHg], respectively, and the differences were statistically significant (t=3.258, 2.148; all P<0.05). In ARDSp group, PAP values of severe ARDS neonates was higher than that of moderate ARDS neonates, and the difference was statistically significant (t=2.424, P=0.021). In ARDSexp group, PAP values of severe ARDS neonates were higher than that of mild [(37.8±6.5) mmHg] and moderate ARDS neonates, respectively, while PAP values of moderate ARDS neonates was higher than that of mild ARDS neonates, and all the differences were statistically significant (t=14.060, 4.891, 5.629; all P<0.001). ④Pearson correlation analysis showed that there was a positive linear correlation between OI and PAP in 78 ARDS neonates (r=0.720, P<0.001). ⑤PAP values of neonates in ARDSp and ARDSexp group after respiratory support of 0, 24, 48, 72, 96 h and pre-extubation were higher than those of neonates at the corresponding hourly age after birth in control group, respectively, and the differences were statistically significant (t=16.920, 21.600, 27.200, 24.440, 21.670, 18.690; t=11.380, 24.680, 37.800, 15.670, 14.460, 18.060; all P<0.001). PAP values of neonates in ARDSexp group after 0, 48, 72, 96 h of respiratory support were lower than those in ARDSp group, but higher than that in ARDSp group after 24 h of respiratory support, and all the differences were statistically significant (t=5.136, 4.829, 8.197, 6.691, 7.483, all P<0.001). Conclusions The PAP of perinatal stage neonates with ARDS increased in varying degrees, and its increased degree was related to the severity of ARDS. The respiratory mechanics paramaters and PAP of ADRSp neonates were different from ADRSexp neonates, PAP can be used as a judgement indicator of the severity and prognosis of ARDS. Key words: Respiratory distress syndrome, newborn; Hypertension, pulmonary; Persistent fetal circulation syndrome; Respiratory mechanics; Perinatology; Lung injury; Infant, newbron

BackgroundDespite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine. Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of transplanted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.ResultsIn this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within seven days after the injury, we found that arterial blood oxygen saturation (SpO2) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2) amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A histological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.ConclusionsThis modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was officially declared a global pandemic on March 11, 2020, by the World Health Organization (WHO). The majority of patients with COVID-19 have mild disease, but approximately 14% develop severe respiratory failure and acute respiratory distress syndrome (ARDS), which is associated with high mortality.1–3 Extracorporeal membrane oxygenation (ECMO) could potentially improve survival in COVID-19-associated severe ARDS and has been incorporated in the WHO recommendation for management of severe COVID-19 disease.4–8 In this issue of ASAIO J, Slepian et al.9 report on the early experience of a multicenter cohort of patients undergoing ECMO for COVID-19 severe respiratory or cardiorespiratory failure. Their study, the largest cohort of COVID ECMO patients to date, describes 32 patients who were provided extracorporeal support either with veno-venous (VV), veno-arterial-venous (VAV), or veno-arterial (VA) ECMO. This initial description provides some insights into the use of ECMO for COVID-19 disease. Notably, the authors provide a glimpse at the median duration of ECMO in the five patients successfully weaned from ECMO (8 days, interquartile range [IQR] = 2–5), in addition to spending several days in endotracheally intubated before initiation of ECMO (median = 4 days, IQR = 2–5). Further, there is a trend toward higher mortality in those patients who require VA-ECMO or VAV-ECMO, in contrast to those patients who only require VV-ECMO, which could potentially be explained by the concomitant cardiac component of their COVID-19 disease, as well as the likely low-flow state and end-organ hypoperfusion before initiating VA-ECMO. However, as the authors note, outcomes are unclear from this cohort as the majority of the patients in the cohort were still receiving ECMO at the time of publication. The report is also limited in that detailed data on patient characteristics and detailed ventilatory data before the provision of ECMO are challenging to come by. These data will be crucial for further tailoring of both ECMO referral and cannulation criteria to identify those most likely to benefit from ECMO support.9 There is currently limited guidance on ECMO use and patient selection in a pandemic surge, particularly for COVID-19. The role of ECMO depends not only on patient factors (such as disease severity) but also on resource availability, as it consumes a large portion of hospital, critical care, and personnel resources.10–13 Moreover, ECMO capacity at these levels of systemic stress may be very limited at centers capable of providing this technology. ECMO growth was catalyzed following the efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure trial successfully demonstrating a mortality benefit in patients referred to an ECMO center for respiratory failure as well as the influenza A (H1N1) viral pandemic in 2009.14–16 Data on the effectiveness of ECMO during previous coronavirus outbreaks, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), remains limited, particularly during SARS. ECMO for MERS demonstrated an association with improved survival.17 Based on this historical experience, it is plausible that ECMO may improve survival outcomes for selected COVID-19 patients with severe ARDS. Given the significant resources required to provide ECMO, it is conceivable that during a pandemic it may become too burdensome to the system to be possible or justifiable. Principles of precision clinical medicine should be applied to patient selection and determining who is likely to most benefit from ECMO support during the COVID-19 pandemic. Early reports have determined several patient factors that are associated with high mortality in COVID-19, which include advanced age (>65 years), presence of comorbidities, extrapulmonary organ failures (assessed through Sequential Organ Failure Assessment score), hyperinflammation (elevated C-reactive protein, ferritin, or d-dimer), leukopenia, and myocardial injury (elevated troponin).18,19 Patients with one or more of the aforementioned risk factors for poor outcomes are less likely to be successfully supported with VV-ECMO. Eligible patients who develop COVID-19-related myocarditis leading to refractory cardiogenic shock may benefit from VA-ECMO, shown to confer survival benefit in patients with isolated myocarditis.20–22 Prospectively validated survival prediction models at ECMO initiation (e.g., RESP and PRESET scores) can assist in the assessment of candidacy for ECMO; however, these scores have not specifically been validated for COVID-19-associated ARDS.23,24 Initial criteria for consideration for ECMO should be based on current evidence and guidance. Patients with very severe ARDS who have been invasively ventilated for 7 days or less meeting the ECMO to rescue lung injury in severe ARDS (EOLIA) trial criteria and recent Extracorporeal Life Support Organization (ELSO) general guidance (ratio of arterial oxygen partial pressure to fractional inspired oxygen [PaO2:FiO2] <50 mmHg for >3 hours, or PaO2:FiO2 <80 mmHg for >6 hours or pH <7.25 with partial pressure of carbon dioxide [PCO2] ≥60 mmHg for more than 6 hours)5,10 without extrapulmonary organ failures could be considered for ECMO support. It is likely that these criteria can be further refined. We know that VV-ECMO is able to provide two major benefits to patients with ARDS. The first is that it can improve oxygenation when the patient has exhausted conventional strategies.5,25 The second, and likely more important mechanism, is that it facilitates extended lung-protective ventilation for patients who are already receiving conventional lung-protective ventilation. The EOLIA trial suggested that patients who were hypercarbic despite maximizing lung-protective ventilation were the group of patients with the greatest survival benefit that ECMO facilitates lung protection through a reduction in driving pressure and mechanical power.5 Patients with COVID-19-associated ARDS often present with notable hypoxemia, yet some may have relatively well-preserved lung compliance.26 The majority of these patients could potentially be managed with conventional methods and without ECMO unless compliance worsens (e.g., due to worsening underlying pathology, patient self-inflicted lung injury, or ventilator-induced lung injury) or hypoxemia is very severe and refractory to conventional management. These are the patients who are most likely to benefit from facilitated lung rest through VV-ECMO. Given the complexity of patient selection, a multidisciplinary approach to patient selection should be undertaken. Collaboration between ECMO centers is crucial to ensure appropriate service delivery and capacity to those patients with confirmed COVID-19 ARDS. Thorough assessment before accepting a patient for ECMO will also ensure that ECMO should only be considered after all conventional measures (lung-protective ventilation, moderate-to-high levels of positive-end expiratory pressure as tolerated, prone positioning, possible neuromuscular blockade, and negative fluid balance, as appropriate) fail to maintain adequate oxygenation and ventilation.27,28 Collaborative decision making between referring centers and the ECMO centers could potentially increase precision of clinical practice by reducing variabilities in the management of ARDS. The decision to offer or decline ECMO during COVID-19 pandemic is a difficult one. ECMO centers need to be highly selective aiming to enhance the precision of individual treatment benefit. This approach will potentially allow judicious planning, resource allocation, and a safe delivery of ECMO service. Prospective data will enable clinicians to better characterize this disease and successfully personalize therapies including ECMO.

The cellular communication network factor 1 (CCN1) is a matricellular protein that can modulate multiple tissue responses, including inflammation and repair. We have previously shown that adenoviral overexpression of Ccn1 is sufficient to cause acute lung injury in mice. We hypothesized that CCN1 is present in the airspaces of lungs during the acute phase of lung injury, and higher concentrations are associated with acute respiratory distress syndrome (ARDS) severity. We tested this hypothesis by measuring 1) CCN1 in bronchoalveolar lavage fluid (BALF) and lung homogenates from mice subjected to ventilation-induced lung injury (VILI), 2) Ccn1 gene expression and protein levels in MLE-12 cells (alveolar epithelial cell line) subjected to mechanical stretch, and 3) CCN1 in BALF from mechanically ventilated humans with and without ARDS. BALF CCN1 concentrations and whole lung CCN1 protein levels were significantly increased in mice with VILI (n = 6) versus noninjured controls (n = 6). Ccn1 gene expression and CCN1 protein levels were increased in MLE-12 cells cultured under stretch conditions. Subjects with ARDS (n = 77) had higher BALF CCN1 levels compared with mechanically ventilated subjects without ARDS (n = 45) (P < 0.05). In subjects with ARDS, BALF CCN1 concentrations were associated with higher total protein, sRAGE, and worse [Formula: see text]/[Formula: see text] ratios (all P < 0.05). CCN1 is present in the lungs of mice and humans during the acute inflammatory phase of lung injury, and concentrations are higher in patients with increased markers of severity. Alveolar epithelial cells may be an important source of CCN1 under mechanical stretch conditions.

Endemic Fungal Infections in Solid Organ Transplantation

Objective To compare survival of patients with acute respiratory distress syndrome after corrective cardiac surgery treated by high-frequency oscillatory ventilation with pulmonary hypertension or without pulmonary hypertension.Methods Among 10827 patients,64 with refractory acute respiratory distress syndrome were ventilated with high-frequency oscillatory ventilation.Patients with significant uncorrected residual lesions were not included.The patients were grouped according to cardiac diagnosis:group Ⅰ (n =33),non-pulmonary hypertension patients; group Ⅱ (n =31),pulmonary hypertension patients.The demographic data,respiratory and circulatory parameters were recorded.The two groups were evaluated for survival rates at discharge as the primary outcome.Results There were no significant differences between the groups with respect to age,weight,central venous pressure,left atrial pressure.The mean duration of high-frequency oscillatory ventilation was significantly shorter in group Ⅰ than that in group Ⅱ [(104.89 ± 53.47)h vs (386.49 ± 125.36)h,P＜0.05].The patients in group Ⅱ showed higher mortality rate than that in group Ⅰ [7 vs.20 (21.2％ vs.64.5％)(P＜0.05)].Conclusions High-frequency oscillatory ventilation therapy for severe postoperative acute respiratory distress syndrome is effective following cardiac surgery. Key words: Heart defects, congenital; Acute respiratory distress syndrome; High-frequency oscillatory ventilation; Cardiac Surgical Procedures;

The Right Ventricle in COVID-19 Lung Injury: Proposed Mechanisms, Management, and Research Gaps

Acute Respiratory Distress Syndrome (ARDS) is a critical form of Acute Lung Injury (ALI), challenging clinical diagnosis and severity assessment. This study evaluates the potential utility of various hematological markers in burn-mediated ARDS, including Neutrophil-to-Lymphocyte Ratio (NLR), Mean Platelet Volume (MPV), MPV-to-Lymphocyte Ratio (MPVLR), Platelet count, and Platelet Distribution Width (PDW). Employing a retrospective analysis of data collected over 12 years, this study focuses on the relationship between these hematological markers and ARDS diagnosis and severity in hospitalized patients. The study establishes NLR as a reliable systemic inflammation marker associated with ARDS severity. Elevated MPV and MPVLR also emerged as significant markers correlating with adverse outcomes. These findings suggest these economical, routinely measured markers can enhance traditional clinical criteria, offering a more objective approach to ARDS diagnosis and severity assessment. Hematological markers such as NLR, MPV, MPVLR, Platelet count, and PDW could be invaluable in clinical settings for diagnosing and assessing ARDS severity. They offer a cost-effective, accessible means to improve diagnostic accuracy and patient stratification in ARDS. However, further prospective studies are necessary to confirm these findings and investigate their integration with other diagnostic tools in diverse clinical settings.

Commentary: Who and when to leave behind: Difficult decisions around extracorporeal membrane oxygenation selection in coronavirus disease 2019

BackgroundPrevious investigations have presumed a potential therapeutic effect of statin therapy in patients with acute respiratory distress syndrome (ARDS). Statins are expected to attenuate inflammation in the lungs of patients with ARDS due to their anti-inflammatory effects. Clinical investigations of the role of statin therapy have revealed contradictory results. This study aimed to investigate whether pretreatment and continuous therapy with statins in patients with sepsis-associated ARDS are associated with 28-day survival according to disease severity (mild, moderate, or severe).MethodsPatients with sepsis-associated ARDS from the surgical intensive care were enrolled in this prospective observational investigation. ARDS was classified into three groups (mild, moderate, and severe); 28-day mortality was recorded as the primary outcome variable and organ failure was recorded as secondary outcome variable. Sequential Organ Failure Assessment scores and the requirements for organ support were evaluated throughout the observational period to assess organ failure.Results404 patients with sepsis-associated ARDS were enrolled in this investigation. The distribution of the ARDS subgroups was 13 %, 59 %, and 28 % for mild, moderate, and severe disease, respectively. Statin therapy improved 28-day survival exclusively in the patients with severe ARDS compared with patients without statin therapy (88.5 % and 62.5 %, respectively; P = 0.0193). To exclude the effects of several confounders, we performed multivariate Cox regression analysis, which showed that statin therapy remained a significant covariate for mortality (hazard ratio, 5.46; 95 % CI, 1.38–21.70; P = 0.0156). Moreover, after carrying a propensity score-matching in the severe ARDS cohort, Kaplan-Meier survival analysis confirmed the improved 28-day survival among patients with statin therapy (P = 0.0205). Patients with severe ARDS who received statin therapy had significantly more vasopressor-free days compared with those without statin therapy (13 ± 7 and 9 ± 7, respectively; P = 0.0034), and they also required less extracorporeal membrane oxygenation (ECMO) therapy and had more ECMO-free days (18 ± 9 and 15 ± 9, respectively; P = 0.0873).ConclusionsThis investigation suggests a beneficial effect of continuous statin therapy in patients with severe sepsis-associated ARDS and a history of prior statin therapy. Further study is warranted to elucidate this potential effect.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0368-6) contains supplementary material, which is available to authorized users.

Defining Right Ventricular Dysfunction in Acute Respiratory Distress Syndrome

The extent of in vivo damage to the alveolar-capillary membrane in patients with primary lung injury remains unclear. In cases of ARDS related to COVID-19 and Influenza type A, the complexity of the damage increases further, as viral pneumonia cannot currently be treated with a causal approach. Our primary goal is to enhance the understanding of Acute Respiratory Distress Syndrome (ARDS) by demonstrating damage to the alveocapillary membrane in critically ill patients with COVID-19 and influenza type A. We will achieve this by measuring the levels of proteins and albumin in bronchoalveolar fluid (BAL) and serum. Our secondary objective is to assess patient outcomes related to elevated protein and albumin levels in both BAL and blood serum, which will deepen our understanding of this complex condition. Bronchoalveolar lavage (BAL) fluid and serum samples were meticulously collected from a total of 64 patients, categorized into three distinct groups: 30 patients diagnosed with COVID-19-related acute respiratory distress syndrome (ARDS), 14 patients with influenza type A (H1N1 strain), also experiencing ARDS, and a control group consisting of 20 patients who were preoperatively prepared for elective surgical procedures without any diagnosed lung disease. The careful selection and categorization of patients ensure the robustness of our study. BAL samples were taken within the first 24 hours following the commencement of invasive mechanical ventilation in the intensive care unit, alongside measurements of serum albumin levels. In the control group, BAL and serum samples were collected after the induction of general endotracheal anaesthesia. Patients in the COVID-19 group are significantly older than those in the Influenza type A (H1N1) group, with median ages of 72.5 years and 62 years, respectively (p < 0.01, Mann-Whitney U test). Furthermore, serum albumin levels (measured in g/L) revealed significant differences across all three groups in the overall sample, yielding a p-value of less than 0.01 according to ANOVA. In terms of treatment outcomes, serum albumin levels also exhibited a significant correlation, with a p-value of 0.03 (Mann-Whitney U test). A reduction in serum albumin levels (below 35 g/L), combined with elevated protein levels in bronchoalveolar lavage (BAL), serves as a predictor of poor outcomes in patients with acute respiratory distress syndrome (ARDS), as indicated by a p-value of less than 0.01 (ANOVA). Our findings indicate that protein and albumin levels in bronchoalveolar lavage (BAL) fluid are elevated in severe acute respiratory distress syndrome (ARDS) cases. This suggests that BAL can effectively evaluate protein levels and fractions, which could significantly assist in assessing damage to the alveolocapillary membrane. Additionally, the increased albumin levels in BAL, often accompanied by a decrease in serum albumin levels, may serve as a valuable indicator of compromised integrity of the alveolar-capillary membrane in ARDS, with potential implications for patient care.