Severe COVID-19 ARDS Treated by Bronchoalveolar Lavage with Diluted Exogenous Pulmonary Surfactant as Salvage Therapy: In Pursuit of the Holy Grail?

Ruaro, Barbara; Confalonieri, Paola; Pozzan, Riccardo; Tavano, Stefano; Mondini, Lucrezia; Baratella, Elisa; Pagnin, Alessandra; Lerda, Selene; Geri, Pietro; Biolo, Marco; Confalonieri, Marco; Salton, Francesco

doi:10.3390/jcm11133577

Cited by 16 publications

(22 citation statements)

References 40 publications

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“…92,93 Early clinical studies have been initiated with some apparent success. 93,94 Overall, a better understanding of the biophysical and physiological properties of surfactant could contribute to the development of strategies that target surfactant dysfunction in ARDS.…”

Section: Acute Respiratory Distress Syndromementioning

confidence: 99%

“…It has dramatically increased the incidence of ARDS-type illnesses and highlights the lack of accepted suitable pharmacological therapies . For the most part, treatment for ARDS has tended to consist largely of supportive measures such as mechanical ventilation. , COVID-19 could provide a unique opportunity for testing the efficacy of surfactant therapy with severe cases, because it is a single direct form of ARDS. , Early clinical studies have been initiated with some apparent success. , Overall, a better understanding of the biophysical and physiological properties of surfactant could contribute to the development of strategies that target surfactant dysfunction in ARDS.…”

Section: Why Study Pulmonary Surfactant?mentioning

confidence: 99%

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Pulmonary Surfactant: A Mighty Thin Film

Possmayer,

Zuo,

Veldhuizen

et al. 2023

Chem. Rev.

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Pulmonary surfactant is a critical component of lung function in healthy individuals. It functions in part by lowering surface tension in the alveoli, thereby allowing for breathing with minimal effort. The prevailing thinking is that low surface tension is attained by a compression-driven squeeze-out of unsaturated phospholipids during exhalation, forming a film enriched in saturated phospholipids that achieves surface tensions close to zero. A thorough review of past and recent literature suggests that the compression-driven squeeze-out mechanism may be erroneous. Here, we posit that a surfactant film enriched in saturated lipids is formed shortly after birth by an adsorptiondriven sorting process and that its composition does not change during normal breathing. We provide biophysical evidence for the rapid formation of an enriched film at high surfactant concentrations, facilitated by adsorption structures containing hydrophobic surfactant proteins. We examine biophysical evidence for and against the compressiondriven squeeze-out mechanism and propose a new model for surfactant function. The proposed model is tested against existing physiological and pathophysiological evidence in neonatal and adult lungs, leading to ideas for biophysical research, that should be addressed to establish the physiological relevance of this new perspective on the function of the mighty thin film that surfactant provides.

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Section: Acute Respiratory Distress Syndromementioning

confidence: 99%

Section: Why Study Pulmonary Surfactant?mentioning

confidence: 99%

Pulmonary Surfactant: A Mighty Thin Film

Possmayer,

Zuo,

Veldhuizen

et al. 2023

Chem. Rev.

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“…Another solution for rapid screening is to use medical imaging, such as chest X-ray images or computed tomography (CT) scanners [ 2 ]. In addition, some methods have also been proposed for the treatment of COVID-19 [ 3 , 4 ]. In medical image analysis, many image-based artificial intelligence approaches have been developed to help combat the disease, including automatic diagnosis, segmentation, and prognosis.…”

Section: Introductionmentioning

confidence: 99%

COVID-19 Infection Segmentation and Severity Assessment Using a Self-Supervised Learning Approach

Song

Liu

et al. 2022

Diagnostics

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Background: Automated segmentation of COVID-19 infection lesions and the assessment of the severity of the infections are critical in COVID-19 diagnosis and treatment. Based on a large amount of annotated data, deep learning approaches have been widely used in COVID-19 medical image analysis. However, the number of medical image samples is generally huge, and it is challenging to obtain enough annotated medical images for training a deep CNN model. Methods: To address these challenges, we propose a novel self-supervised deep learning method for automated segmentation of COVID-19 infection lesions and assessing the severity of infection, which can reduce the dependence on the annotation of the training samples. In the proposed method, first, many unlabeled data are used to pre-train an encoder-decoder model to learn rotation-dependent and rotation-invariant features. Then, a small amount of labeled data is used to fine-tune the pre-trained encoder-decoder for COVID-19 severity classification and lesion segmentation. Results: The proposed methods were tested on two public COVID-19 CT datasets and one self-built dataset. Accuracy, precision, recall, and F1-score were used to measure classification performance and Dice coefficient was used to measure segmentation performance. For COVID-19 severity classification, the proposed method outperformed other unsupervised feature learning methods by about 7.16% in accuracy. For segmentation, when the amount of labeled data was 100%, the Dice value of the proposed method was 5.58% higher than that of U-Net.; in 70% of the cases, our method was 8.02% higher than U-Net; in 30% of the cases, our method was 11.88% higher than U-Net; and in 10% of the cases, our method was 16.88% higher than U-Net. Conclusions: The proposed method provides better classification and segmentation performance under limited labeled data than other methods.

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“…Late in 2019 an infectious outbreak that caused pneumonia and acute respiratory distress syndrome (ARDS) occurred in Wuhan, Hubei Province, China resulting in the World Health Organization (WHO) naming the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and the condition Coronavirus disease 2019 (COVID-19) [ 1 , 2 , 3 ]. By March 2020, the infection had spread around the world and was declared to be a pandemic [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Factors Associated with COVID-19 from an International Registry of Primarily Japanese Patients

et al. 2022

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Aims: We developed an international registry to examine cardiovascular complications of COVID-19. Methods: A REDCap form was created in March 2020 at Mayo Clinic in collaboration with the International Society of Cardiomyopathy, Myocarditis and Heart Failure (ISCMF) and data were entered from April 2020 through April 2021. Results: Of the 696 patients in the COVID-19 Registry, 411 (59.2%) were male and 283 (40.8%) were female, with a sex ratio of 1.5:1 male to female. In total, 95.5% of the patients were from Japan. The average age was 52 years with 31.5% being >65 years of age. COVID-19 patients with a history of cardiovascular disease (CVD) had more pre-existing conditions including type II diabetes (p < 0.0001), cancer (p = 0.0003), obesity (p = 0.001), and kidney disease (p = 0.001). They also had a greater mortality of 10.1% compared to 1.7% in those without a history of CVD (p < 0.0001). The most common cardiovascular conditions in patients with a history of CVD were hypertension (33.7%), stroke (5.7%) and arrhythmias (5.1%). We found that troponin T, troponin I, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), C-reactive protein (CRP), IL-6 and lambda immunoglobulin free light chains (Ig FLC) were elevated above reference levels in patients with COVID-19. Myocarditis is known to occur mainly in adults under the age of 50, and when we examined biomarkers in patients that were ≤50 years of age and had no history of CVD we found that a majority of patients had elevated levels of troponin T (71.4%), IL-6 (59.5%), creatine kinase/CK-MB (57.1%), D-dimer (57.8%), kappa Ig FLC (75.0%), and lambda Ig FLC (71.4%) suggesting myocardial injury and possible myocarditis. Conclusions: We report the first findings to our knowledge of cardiovascular complications from COVID-19 in the first year of the pandemic in a predominantly Japanese population. Mortality was increased by a history of CVD and pre-existing conditions including type II diabetes, cancer, obesity, and kidney disease. Our findings indicate that even in cases where no abnormalities are found in ECG or ultrasound cardiography that myocardial damage may occur, and cardiovascular and inflammatory biomarkers may be useful for the diagnosis.

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Severe COVID-19 ARDS Treated by Bronchoalveolar Lavage with Diluted Exogenous Pulmonary Surfactant as Salvage Therapy: In Pursuit of the Holy Grail?

Cited by 16 publications

References 40 publications

Pulmonary Surfactant: A Mighty Thin Film

Pulmonary Surfactant: A Mighty Thin Film

COVID-19 Infection Segmentation and Severity Assessment Using a Self-Supervised Learning Approach

Cardiovascular Factors Associated with COVID-19 from an International Registry of Primarily Japanese Patients

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