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1.
Clin Chim Acta ; 537: 140-145, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2085986

ABSTRACT

BACKGROUND: Surfactant protein-D (SP-D) is a lung-resident protein that has emerged as a potential biomarker for COVID-19. Previous investigations on acute respiratory distress syndrome patients demonstrated a significant increment of SP-D serum levels in pathological conditions. Since SP-D is not physiologically permeable to alveoli-capillary membrane and poorly expressed by other tissues, this enhancement is likely due to an impairment of the pulmonary barrier caused by prolonged inflammation. METHODS: A retrospective study on a relatively large cohort of patients of Hospital Pio XI of Desio was conducted to assess differences of the hematic SP-D concentrations among COVID-19 patients and healthy donors and if SP-D levels resulted a risk factor for disease severity and mortality. RESULTS: The first analysis, using an ANOVA-model, showed a significant difference in the mean of log SP-D levels between COVID-19 patients and healthy donors. Significant variations were also found between dead vs survived patients. Results confirm that SP-D concentrations were significantly higher for both hospitalized COVID-19 and dead patients, with threshold values of 150 and 250 ng/mL, respectively. Further analysis conducted with Logistic Mixed models, highlighted that higher SP-D levels at admission and increasing differences among follow-up and admission values resulted the strongest significant risk factors of mortality (model predictive accuracy, AUC = 0.844). CONCLUSIONS: The results indicate that SP-D can be a predictive marker of COVID-19 disease and its outcome. Considering its prognostic value in terms of mortality, the early detection of SP-D levels and its follow-up in hospitalized patients should be considered to direct the therapeutic intervention.


Subject(s)
COVID-19 , Pulmonary Surfactant-Associated Protein D , Humans , COVID-19/diagnosis , Retrospective Studies , SARS-CoV-2 , Biomarkers
2.
Tissue Engineering - Part A ; 28:324-325, 2022.
Article in English | EMBASE | ID: covidwho-2062832

ABSTRACT

Purpose/Objectives: <Most used lower respiratory tract models consist of cell monolayers which lack of tissue and organ level response and of in-vivo phenotype. Ex-vivo lung tissues have short viability and limited availability. Lung organoids, which recapitulates better the 3D cellular complex structures, architecture, and in-vivo function, fail to reach maturity even after 85 -185 days of culture. Therefore, these models have a limited use to study fetal lung diseases. Other lung models, consist of only one structure of the lower track, such as bronchial tubes or alveoli, but fail to recapitulate the whole organ structure. In this work, cell microenvironment was used to promote the self-organization of epithelial and mesenchymal cells into macro-structures, aiming to mimic the whole and adult lower respiratory tract model> Methodology: <Different parts of the microenvironment were considered to create a compliant matrix. Alginate-Gelatin hydrogels were used for 3D encapsulation of mesenchymal origin cells. This hydrogel provided a stiffness like the one on the lung. Base membrane zone proteins were used to induce the attachment and guidance of epithelial cells into 3D structures. The interactions between both cell types, further guided them into lung fate. The morphology of resulting organoids was analyzed using immunostaining and confocal microscopy, LSM710, with the purpose of evaluate polarization, protein markers, and different cell populations. Quantitative PCR was performed to evaluate and compare the expression of lung fate genes with traditional cell monocultures.> Results: <The engineered microenvironment and protocol development done in this work resulted in macro-scale structures, in which branching morphogenesis occurred at day 21. Different structures were identified in the organoid including bronchial tube, bronchioles, and alveoli. Polarization of the organoids was confirmed by visualization of E-cadherin, and ZO-1. Expression of Surfactant Protein B and C into the organoids confirmed the presence of alveolar type II cells, which are only present in the later development stage. Surfactant Protein B, Transmembrane protease, serine 2, TMPRSS-2, and Angiotensin-converting enzyme 2, ACE2 were found to be significantly higher expressed into the organoids in comparison with traditional epithelial cells monolayers.> Conclusion/Significance: <Growth factors are normally used to induce the fate of stem cells into lung organoids;however, these fail to reach maturity. Here, we developed a new methodology to induce the formation of the organoids based on the cell microenvironment. The resulting organoids require less time for development. The initial stage of adult cells can be modulated through culture conditions induce a 3D structure like the adult lung. As such, these organoids have the potential to be used for modeling adult diseases and to develop specific models from patient cells, which is one step forward to personalized medicine. SFTPB is one of the main proteins which facilitates the breathing process. Its high expression into our model may indicate that breathing occurs into our lung organoids. The higher expression of TMPRSS-2 and ACE2 into the organoids has a major significance in the field of virology since both proteins are the mainly entrance of SARS-CoV-2, and influenza H1N1.>.

3.
Biomed J ; 45(4): 615-628, 2022 08.
Article in English | MEDLINE | ID: covidwho-2060465

ABSTRACT

The lives of thousands premature babies have been saved along the last thirty years thanks to the establishment and consolidation of pulmonary surfactant replacement therapies (SRT). It took some time to close the gap between the identification of the biophysical and molecular causes of the high mortality associated with respiratory distress syndrome in very premature babies and the development of a proper therapy. Closing the gap required the elucidation of some key questions defining the structure-function relationships in surfactant as well as the particular role of the different molecular components assembled into the surfactant system. On the other hand, the application of SRT as part of treatments targeting other devastating respiratory pathologies, in babies and adults, is depending on further extensive research still required before enough amounts of good humanized clinical surfactants will be available. This review summarizes our current concepts on the compositional and structural determinants defining pulmonary surfactant activity, the principles behind the development of efficient natural animal-derived or recombinant or synthetic therapeutic surfactants, as well as a the most promising lines of research that are already opening new perspectives in the application of tailored surfactant therapies to treat important yet unresolved respiratory pathologies.


Subject(s)
Pulmonary Surfactants , Respiratory Distress Syndrome, Newborn , Respiratory Distress Syndrome , Animals , Humans , Infant, Newborn , Pulmonary Surfactants/chemistry , Pulmonary Surfactants/therapeutic use , Respiratory Distress Syndrome, Newborn/drug therapy , Surface-Active Agents/pharmacology , Surface-Active Agents/therapeutic use
4.
Chest ; 162(4):A1868, 2022.
Article in English | EMBASE | ID: covidwho-2060878

ABSTRACT

SESSION TITLE: Drug-Induced Lung Injury Pathology Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Acute eosinophilic pneumonia (AEP) is an atypical cause of acute hypoxic respiratory failure in adults, however if not identified can prove to be fatal. It can all be a COVID19 mimic during the pandemic. AEP has several causes, such as inhalational drugs, infections and various pharmaceuticals. Often, patients will have an acute respiratory syndrome for less than one-month, pulmonary infiltrates on chest computed tomography (CT) or radiography (CXR), in addition to bronchoalveolar lavage (BAL) with more than 25% of eosinophils. CASE PRESENTATION: A 79 y/o man underwent an elective total knee replacement complicated by acute lower limb ischemia from an occluded bypass graft. He developed methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococcus (VRE) joint and soft tissue infection of the lower extremity. He was prescribed a 6-week course of Daptomycin. He presented about 3 weeks into treatment with shortness of breath. He was initially diagnosed with acute on chronic congestive heart failure (CHF) exacerbation and COVID negative. He was initially treated with diuretics. He developed acute renal failure requiring dialysis and acute hypoxic respiratory failure requiring intubation. CXR revealed bilateral lung infiltrates with BAL having 80% eosinophils, eosinophilia and urinalysis positive for eosinophils. Daptomycin was discontinued and he was started on systemic steroids for a two-week course. He was successfully extubated 5 days after diagnosis of AEP and was subsequently discharged to a rehabilitation facility on lifelong Doxycycline for MRSA prosthetic joint infection prophylaxis. DISCUSSION: AEP related to Daptomycin was first reported in 2007, in a patient that developed the condition after receiving treatment for endocarditis. Daptomycin caused an inflammatory reaction within the lungs, due to an accumulation of the drug within the pulmonary surfactant. Our case report patient met all components for AEP diagnosis, in addition to symptom onset being approximately 3 weeks into treatment. The ultimate treatment for AEP is to stop the reversible cause, if identifiable, along with glucocorticoids and symptomatic support. Prognosis for patients with AEP is excellent when diagnosis is prompt, and usually infiltrates are resolved within 1 month without long term adverse pulmonary effects. Our patient was discharged to an acute rehab facility without supplemental oxygen therapy and continues to improve from functional standpoint. This case a definite cause of AEP from Daptomycin presented as COVID19 pneumonia mimic. It highlights the importance of rapid diagnosis to prevent morbidity and mortality. CONCLUSIONS: The differential in a patient with acute hypoxic respiratory failure is numerous, especially during the COVID19 pandemic. During these challenging times, it is important to think of atypical causes, such as AEP to improve the patient's clinical status. Reference #1: Allen JN, Pacht ER, Gadek JE, Davis WB. Acute Eosinophilic Pneumonia as a Reversible Cause of Noninfectious Respiratory Failure. N Engl J Med. 1989;321:569-574 Reference #2: Hayes Jr. D, Anstead MI, Kuhn RJ. Eosinophilic pneumonia induced by daptomycin. J Infect. 2007;54(4):e211-213. Reference #3: Rachid M, Ahmad K, Saunders-Kurban M, Fatima A, Shah A, Nahhas A. Daptomycin-Induced Acute Eosinophilic Pneumonia: Late Onset and Quick Recovery. Case Reports in Pulmonology. 2017. DISCLOSURES: No relevant relationships by Moses Bachan No relevant relationships by Zinobia Khan No relevant relationships by Kaitlyn Mehern

5.
Chest ; 162(4):A1866, 2022.
Article in English | EMBASE | ID: covidwho-2060877

ABSTRACT

SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Interstitial pneumonitis (ILD) is inflammation of lung interstitium leading to scarring and pulmonary fibrosis. Various etiologies include idiopathic, connective tissue disorders, sarcoidosis and drug induced1. Many chemotherapy agents have been implicated in drug related ILD such as bleomycin, taxanes. However, newer chemotherapeutic drugs such as molecular agents such as anti-VEGF, anti-EGFR (panitumumab) could be causative of drug induced ILD. CASE PRESENTATION: A 75-year-old female with stage IV sigmoid colon cancer treated with surgery, adjuvant FOLFOX chemotherapy and Panitumumab. She presented to the emergency department with shortness of breath and hypoxia after known COVID-19 exposure. Initial imaging with chest radiography showed bilateral ground glass opacities. A chest CT pulmonary embolism protocol was negative for pulmonary embolism but showed bilateral ground glass opacities (GGOs) and some interstitial thickening (L>R) not typical of COVID-19 infection. She was treated with remdesivir and dexamethasone, however her oxygen requirements continued to rapidly escalate. A repeat CT chest without contrast showed bilateral asymmetric interstitial thickening and GGOs. Given persistence of CT chest abnormalities, workup for interstitial lung disease was initiated. The results include ANA titer 1:80, otherwise negative ANCA profile, rheumatoid factor, anti-CCP, Scl-70, Sjogren antibodies. Given clinical history and imaging findings, diagnosis of ILD was suspected, and she was started on solumedrol 1 mg/kg. Her oxygen requirements decreased significantly over the next 2 days, and she was discharged home on oral steroid taper and pneumocystis pneumonia prophylaxis. DISCUSSION: Panitumumab is a fully humanized monoclonal antibody against EGFR. Approved by the US Food and Drug Administration in 2006 for advanced or recurrent colorectal cancer exhibiting wild-type KRAS mutation.2 ILD is rarely reported with panitumumab monotherapy, but higher incidence when used as a combination treatment such as with FOLFOX or FOLFIRI. A Japanese post-marketing surveillance study from 2010-2015 showed an ILD incidence of 1.3% but mortality rates of 51.3%.2 EGFR is expressed on basal cells and non-cilia cells of the bronchioles and type II cells of the alveolus. EGFR mediated mechanisms are important in tissue repair.3 Therefore inhibition of this pathway has been postulated to play a role in development of ILD. Another mechanism was decreased surfactant production by type II cells in pre-clinical study.4,5 ILD secondary to Panitumumab can occur at any point during therapy and up to 1 year after administration of drug.6 The role of infectious processes, in this case, COVID-19 pneumonia, could synergistically worsen ILD presentation. CONCLUSIONS: Although the incidence of ILD is low, the mortality rate is high, therefore early recognition and treatment is associated with improved clinical outcomes. Reference #1: Mudawi D, Heyes K, Hastings R, Rivera-Ortega P, Chaudhuri N. An update on interstitial lung disease. Br J Hosp Med (Lond). Jul 2 2021;82(7):1-14. Reference #2: Osawa M, Kudoh S, Sakai F, et al. Clinical features and risk factors of panitumumab-induced interstitial lung disease: a postmarketing all-case surveillance study. Int J Clin Oncol. Dec 2015;20(6):1063-1071. Reference #3: The FASEB Journal - 2000 - Puddicombe - Involvement of the epidermal growth factor receptor in epithelial repair in asthma.pdf. DISCLOSURES: No relevant relationships by Navitha Ramesh No relevant relationships by Uba Udeh

6.
Chest ; 162(4):A1804, 2022.
Article in English | EMBASE | ID: covidwho-2060865

ABSTRACT

SESSION TITLE: Lung Cancer Imaging Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a lung condition that is caused by a build-up of proteins, fats, and other substances (collectively called surfactants) in the alveoli of the lungs. Here we describe a case of a 47-year-old female diagnosed with PAP, with radiologic features conflicting with Coronavirus Disease 19 (COVID-19) pneumonia. CASE PRESENTATION: The patient is a 47-year-old female with no significant medical history who presents to the outpatient pulmonology clinic for shortness of breath evaluation. She reported that for the past 3-4 months she has been having progressively worsening shortness of breath (SOB) associated with dry cough, and nasal congestion. She reports no recent illness, no history of COVID or COVID exposure, no second-hand smoke exposure, no toxin/chemical exposure, no pets/birds at home. Her SOB has been impacting her lifestyle. Pulmonary function tests showed no obstruction, moderate restriction, mildly decreased diffusion capacity. Computed tomography (CT) of the chest showed multiple ground-glass opacities with septal wall thickening (appears crazy paving pattern) - suggestive of infection or inflammatory process. Infectious/inflammatory work up with HIV, COVID-19, hypersensitivity pneumonitis (HP) panel, autoimmune panel, immunoglobulins, QuantiFERON gold, IgM mycoplasma antibodies was negative. Repeat CT chest in 6 weeks as per patient request, was unchanged from prior. A bronchoscopy was done, bronchoalveolar lavage (BAL) negative for infection - fungal, acid-fast bacilli, Mycobacterium tuberculosis;GMS (Grocott's methenamine silver) stain negative for fungus;negative PCP (Pneumocystis pneumonia);left upper lobe and left lung biopsy showed lung parenchyma with scant amorphous eosinophilic material in alveolar sacs, Periodic Acid-Schiff stain (PAS) stain was positive confirming PAP diagnosis. DISCUSSION: PAP is a rare disease, affecting about 1 person in 100,000 people worldwide, with fewer than 10,000 of them in the United States. The "crazy paving pattern" is characteristic of PAP but recently it has appeared in the list of radiologic findings for COVID 19 pneumonia1,2,3. In these COVID times, these kinds of interactions might make the decision tougher, often leading to misdiagnosis. The decision of diagnosis/treatment should be based on symptoms and their duration, medical history, previous tests, response to treatment. Given our patient never had a COVID infection in the past or current infection, CT chest was typical for PAP with a crazy-paving pattern, no significant subjective/radiological improvement lead us to the diagnosis of PAP with eventual work up with bronchoscopy. CONCLUSIONS: A high index of suspicion is needed for the diagnosis of such rare diseases as PAP, which can be misdiagnosed as COVID-19 pneumonia, given radiological similarities. Early diagnosis and treatment can improve morbidity and mortality of PAP. Reference #1: PAP with COVID-19 Radiology - Differential Diagnosis Discussion, PMID: 33646114 Reference #2: Proteinaceous Lung With COVID-19: The Mimicker, PMID: 34703683 Reference #3: COVID-19 pneumonia: the great radiological mimicker - https://insightsimaging.springeropen.com/articles/10.1186/s13244-020-00933-z DISCLOSURES: No relevant relationships by Ahmad Al-Alwan No relevant relationships by Arundhati Chandini Arjun No relevant relationships by Farhan Khalid no disclosure submitted for Boning Li;No relevant relationships by Rana Prathap Padappayil No relevant relationships by Raghu Tiperneni

7.
Chest ; 162(4):A1773, 2022.
Article in English | EMBASE | ID: covidwho-2060858

ABSTRACT

SESSION TITLE: Drug-Induced Lung Injury Pathology Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Daptomycin is an antibiotic that exerts its bactericidal effect by disrupting multiple aspects of bacterial cell membrane function. It has notable adverse effects including myopathy, rhabdomyolysis, eosinophilic pneumonitis, and anaphylactic hypersensitivity reactions. CASE PRESENTATION: A 46-year-old male with a history of type 2 diabetes presented with a 1-week history of dyspnea and productive cough. 2 weeks prior, he was started on vancomycin for MRSA osteomyelitis of the right foot, but was switched to daptomycin due to vancomycin induced nephrotoxicity. On presentation he was afebrile, tachycardic 100, hypertensive 183/109, tachypneic to 26, hypoxemic 84% on room air, which improved to 94% on nasal cannula. Chest exam noted coarse breath sounds in all fields and pitting edema of lower extremities were present. Labs showed leukocytosis of 15.2/L, Na of 132 mmol/L, and creatinine 3.20mg/dL (normal 1 month prior). COVID-19 testing was negative. Chest X-ray noted new bilateral asymmetric opacifications. Daptomycin was discontinued on day 1 of admission, he was started on IV diuretics and ceftaroline. Further study noted peripheral eosinophilia. Computed tomography of the chest showed bilateral centrally predominant ground-glass infiltrates with air bronchograms and subcarinal and paratracheal lymphadenopathy. On day 4, he underwent bronchoscopy with bronchoalveolar lavage. Cytology noted 4% eosinophil with 43% lymphocytes. Eventually, oxygen requirements and kidney function returned to baseline. He was discharged on ceftaroline for osteomyelitis DISCUSSION: Daptomycin-induced acute eosinophilic pneumonitis (AEP) often results in respiratory failure in the setting of exposure to doses of daptomycin >6mg/kg/day. It is characterized by the infiltration of pulmonary parenchyma with eosinophils and is often associated with peripheral eosinophilia. AEP has been associated with certain chemicals, non-steroidal anti-inflammatory agents, and antibiotics including daptomycin. Renal dysfunction is associated with an increased risk for developing AEP. The mechanism for daptomycin-induced lung injury is unknown but is believed to be related to daptomycin binding to pulmonary surfactant culminating in epithelial injury. Diagnostic criteria include recent daptomycin exposure, fever, dyspnea with hypoxemic respiratory failure, new infiltrates on chest radiography, BAL with > 25% eosinophils, and clinical improvement following daptomycin discontinuation. Our patient met four out of six criteria;we believe that BAL results were due to discontinuing daptomycin days before the procedure was performed. Sometimes stopping daptomycin is enough for recovery, however, steroids may be beneficial and were used in some of the cases reported in the literature CONCLUSIONS: Clinicians should consider AEP in a patient on Daptomycin presenting with respiratory failure, as timely discontinuation favors a good prognosis Reference #1: Uppal P, LaPlante KL, Gaitanis MM, Jankowich MD, Ward KE. Daptomycin-induced eosinophilic pneumonia - a systematic review. Antimicrob Resist Infect Control. 2016;5:55. Published 2016 Dec 12. doi:10.1186/s13756-016-0158-8 Reference #2: Kumar S, Acosta-Sanchez I, Rajagopalan N. Daptomycin-induced Acute Eosinophilic Pneumonia. Cureus. 2018;10(6):e2899. Published 2018 Jun 30. doi:10.7759/cureus.2899 Reference #3: Bartal C, Sagy I, Barski L. Drug-induced eosinophilic pneumonia: A review of 196 case reports. Medicine (Baltimore). 2018;97(4):e9688. doi:10.1097/MD.0000000000009688 DISCLOSURES: No relevant relationships by Chika Winifred Akabusi No relevant relationships by Shazia Choudry No relevant relationships by Hector Ojeda-Martinez No relevant relationships by Mario Torres

8.
Chest ; 162(4):A1192, 2022.
Article in English | EMBASE | ID: covidwho-2060788

ABSTRACT

SESSION TITLE: Rare Genetic Mutations and Anatomical Variants SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a fatal disease affecting older adults that results in progressive scarring of the lung parenchyma. Familial IPF (FPF), defined by disease in two or more first-degree relatives, is estimated to occur in 2–20% of all IPF cases and can present with varying phenotypes which may be difficult to diagnose. Inherited gene variation as well as environmental factors predispose a patient to disease development. Additionally, rare genetic variants in the genes encoding surfactant A (SFTPA1, and SFTPA2) that affect alveolar stability and endoplasmic reticulum stress have been reported in less than 1% of FPF cases. Understanding these genetic variants is essential in the diagnosis and management of patients with FPF. CASE PRESENTATION: A 47-year-old Hispanic male with a history of COVID-19 one year ago (not requiring hospitalization) presented to the hospital for a two-day history of subjective fever and shortness of breath. He was hypoxic requiring oxygen via high flow nasal cannula. He was admitted four months ago for shortness of breath and treated for pneumonia. Since then, he has had chronic dyspnea with exertion. Computed tomography of the chest showed extensive ground glass opacities, worse in the right lung, with basilar and upper lobe honeycombing, and air bronchograms in the bilateral lower lobes. Family history was significant for a mother, maternal aunt, maternal grandfather, and maternal cousin who all died from pulmonary fibrosis. His maternal cousin was treated at our facility, in which genetic sequencing revealed a mutation in SFTPA2, c.697T>C. Our patient was found to have the same genetic mutation. DISCUSSION: The genetic basis of IPF remains poorly understood. Prior studies suggest only 20-30% of FPF cases harbor an identifiable causative genetic variant. Rare variants in two biologic pathways contribute to the known heritability of FPF including pathologic variants in surfactant related genes which cause improper protein trafficking leading to endoplasmic reticulum stress, defects in autophagy, and type II alveolar cell toxicity. SFTPA1 and SFTPA2 variants have been associated with FPF and lung adenocarcinoma in a small number of families and there are few reported cases. While currently the SFTPA2, c.697T>C mutation, previously reported by our group in 2016, is considered a variant of unknown significance, its occurrence in two relatives with serious progressive interstitial lung diseases suggests that it is indeed pathogenic. CONCLUSIONS: Gene sequencing should be considered for all patients with a family history of pulmonary fibrosis as identification of a rare genetic variant may offer guidance to diagnosis, prognostication, and risk stratification when considering lung transplantation as well as identify additional relatives who may be affected by IPF. Reference #1: Kropski JA, Young LR, Cogan JD, et al. Genetic Evaluation and Testing of Patients and Families with Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2017;195(11):1423-1428. doi:10.1164/rccm.201609-1820PP Reference #2: Wang Y, Kuan PJ, Xing C, Cronkhite JT, Torres F, Rosenblatt RL, DiMaio JM, Kinch LN, Grishin NV, Garcia CK. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet. 2009 Jan;84(1):52-9. doi: 10.1016/j.ajhg.2008.11.010. Epub 2008 Dec 18. PMID: 19100526;PMCID: PMC2668050. Reference #3: Pulmonary Fibrosis Due to a Novel Surfactant Protein Mutation R.A. Arciniegas Flores, I.A. Vital, K. Medepalli, D. DeMarzo, M.K. Glassberg Csete, R.A. Alvarez. https://doi.org/10.1164/ajrccm-conference.2019.199.1_Meetings.A5437 DISCLOSURES: No relevant relationships by Roger Alvarez No relevant relationships by Eduardo Lopez Gonzalez No relevant relationships by Anita Singh

9.
Chest ; 162(4):A949, 2022.
Article in English | EMBASE | ID: covidwho-2060737

ABSTRACT

SESSION TITLE: What Lessons Will We Take From the Pandemic? SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Since the emergence of COVID-19, many serious complications have arisen especially in the setting of Acute Respiratory Distress Syndrome (ARDS) in the intensive care unit. Historically, ARDS and mechanical ventilation is associated with higher rates of pneumothorax. It has been well described that ARDS is the result of inflammatory lung injury, with increased activation of circulating neutrophils, complement and proinflammatory mediators leading to loss of surfactant, alveolar atelectasis, and fibrin deposition. This leads to a less compliant lung parenchyma, and higher airway pressures, which has been attributed as a risk factor for pneumothorax. The management of pneumothorax varies depending on the etiology of the pneumothorax. In the case of iatrogenic pneumothorax (i.e. mechanical ventilation), tube thoracostomy is generally recommended, however the size of the chest tube inserted remains less clear. METHODS: This is a multi-center retrospective cohort study of 88 hospitalized patients with a diagnosis of COVID-19 and pneumothorax or pneumomediastinum between the dates of 3/11/2020 to 01/26/2021. Patient demographics, comorbidities, laboratory and hemodynamic data were collected as well as ventilator settings, lung mechanics, and clinical patient outcome data including type of intervention and rate of resolution of pneumothorax. Final statistical analysis is pending. RESULTS: Our preliminary results reveal that there was a higher rate of resolution of pneumothorax with a large bore chest tube (LBCT) compared to a small bore chest tube (SBCT). There was no significant difference in lung compliance or tidal volume in cc/kg between the patients with a resolving pneumothorax compared to the patients with a nonresolving pneumothorax. Overall mortality rate among all patients was 70.4%. CONCLUSIONS: Patients with a large bore chest tube placed are more likely to have resolution of pneumothorax compared to small bore chest tube or serial X-ray. Lung compliance and tidal volume were not significantly different between patients that had a resolving pneumothorax compared to nonresolving pneumothorax. It is important to manage a pneumothorax early on to reduce associated morbidity. CLINICAL IMPLICATIONS: The development of pneumothorax in COVID patients with ARDS has significant associated morbidity and mortality. Utilization of a large bore chest tube may result in improved rates of resolution of pneumothorax. DISCLOSURES: No relevant relationships by Nathalie Antonios No relevant relationships by Colby Baker No relevant relationships by Jessica Johnson No relevant relationships by Karen Sayad

10.
Chest ; 162(4):A938, 2022.
Article in English | EMBASE | ID: covidwho-2060733

ABSTRACT

SESSION TITLE: ECMO and ARDS in COVID-19 Infections SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: The SARS-CoV-2 virus preferentially attacks alveolar Type 2 cells that have the membrane ACE2 receptors. Type 2 cells are the surfactant producing cells in the lung. Damage to Type 2 cells can result in decreased/abnormal surfactant production leading to ARDS and respiratory failure. Surfactant is further inactivated by inflammatory proteins during ARDS. We sought to evaluate the feasibility, safety and tolerability of surfactant therapy in COVID-19 associated ARDS using a synthetic surfactant, lucinactant. METHODS: Open-label, single arm, multicenter study (NCT04389671) in adults with COVID-19 associated ARDS, who have been intubated and on mechanical ventilation (MV) with a P/F ratio <= 300. COVID-19 infection was confirmed by PCR. Lucinactant at a dose of 160 ml (∼80 mg TPL/kg lean body weight) was delivered intratracheally within 7 days of intubation. Retreatment was allowed at >= 6-hour intervals if subjects remained on MV. Assessments included time to deliver the dose, physiologic parameters of oxygenation (P/F, OI, PaO2), FiO2, PaCO2, lung compliance (CL) from baseline (pre-dosing) through day 5 post-dosing. Safety parameters included peri-dosing (PD) events (bradycardia, desaturation, hypotension, regurgitation) and adverse events through 30 days post dosing. RESULTS: 20 subjects were enrolled and 19 received at least one dose. Five subjects received 2 doses of lucinactant. The mean age of subjects was 49 years, 80% were male, 60% were white. The mean time to administer the dose was 31 minutes. FiO2 requirements, PaO2 and PCO2 remained stable throughout the 5-day period post dosing. Baseline mean P/F ratio and standard deviation (SD) was 196 (68), 179 (57) at 12 hours and 193 (61) at day 1 post-dosing, followed by a gradual increase to 223 (105) at day 5. Mean CL increased from 40.5 (16) at baseline to 49.8 (23) at day 5. Seven subjects (37%) died, 6 due to secondary infection and sepsis > 13 days after dosing. Two subjects experienced transient PD events (desaturation, regurgitation). Lucinactant administration in severe ARDS due to COVID-19 was safe and generally well tolerated. The incidence of PD events was low. Stable to improved physiologic parameters of oxygenation were observed post dosing. Increasing the dose and number of administrations may provide additional benefit. CLINICAL IMPLICATIONS: The data support continued study of lucinactant in ARDS patients. DISCLOSURES: Consultant relationship with Windtree Therapeutics Please note: August 2000 Added 03/31/2022 by Carlos Guardia, value=Consulting fee Consultant relationship with Windtree Therapeutics Inc. Please note: August 2000 Added 03/31/2022 by Carlos Guardia, value=Consulting fee Removed 03/31/2022 by Carlos Guardia Advisory Committee Member relationship with Windtree, inc Please note: 4/2021-2/2022 Added 04/04/2022 by Yuh-Chin Huang, value=Grant/Research No relevant relationships Added 04/04/2022 by Peter Morris, value=Consulting fee Removed 04/04/2022 by Peter Morris Employee relationship with Windtree Therapeutics, Inc. Please note: 2008-2022 Added 04/04/2022 by Phillip Simmons, value=Salary Employee relationship with Windtree Therapeutics Please note: 2014 to present Added 04/14/2022 by Steven Simonson, value=Salary

11.
Journal of Pediatric Infectious Diseases ; 2022.
Article in English | Web of Science | ID: covidwho-2042375

ABSTRACT

Objective The epidemiological and clinical characteristics of neonates born to women infected with coronavirus disease 2019 (COVID-19) during pregnancy were assessed, and the correlation between this infection and spontaneous pneumothorax in neonates born to mothers with COVID-19 was evaluated in the present study. Methods Records of 14 neonates in the neonatal intensive care unit with pneumothorax were collected and analyzed. Pregnant women were routinely screened for COVID-19 before birth. This study only included the neonates of mothers positive for severe acute respiratory syndrome coronavirus 2 immunoglobulin Mand immunoglobulin G and developing spontaneous pneumothorax. Antenatal, natal and postnatal risk factors, data related to demographic, epidemiological and clinical characteristics, treatment strategies, and breastfeeding history were obtained from medical records. Results The gestational age of the 14 neonates was 30 to 38 weeks. One male infant was born by normal spontaneous vaginal delivery, while all other infants were born by C-section. Though the mothers did not have a diagnosis of COVID-19 in their charts, they all reported one or more symptoms when interviewed. No mother had received a COVID-19 vaccination before or during pregnancy. No mother had undergone a hospital visit or doctor examination due to suspicion of COVID and COVID polymerase chain reaction test. COVID antibody titers were present during admission to hospital before birth. Conclusion The infants of pregnant cases with symptomatic or asymptomatic COVID-19 may develop respiratory distress and pneumothorax. Observational data obtained from case series similar to what is presented here may be accepted as a potential first step to producing hypotheses to test with preclinical or clinical models if it can be expanded in larger cohorts.

12.
Biomed J ; 45(4): 567-572, 2022 08.
Article in English | MEDLINE | ID: covidwho-2035803

ABSTRACT

In this issue of the Biomedical Journal the reader is provided with an insight into the latest observations and advances in acute kidney injury as well as chronic kidney disease. The current SARS-CoV-2 variants are reviewed, and the role of long non-coding RNA in HIV therapy is explored. Furthermore, the potential of metabolomics as means to diagnose multiple sclerosis as well as tuberculosis is presented. Other topics of this issue include the restoration of the spermatogonial stem cell niche; atherosclerosis and the use of improved ultrasound images; and the effect of transcranial magnetic stimulation in patients with autism spectrum disorder. Finally, it is shown how continuous passive motion can be used as supportive therapeutic approach in children with cerebral palsy, and minimally invasive surgery is presented as valid alternative in cases of spine metastasis.


Subject(s)
Autism Spectrum Disorder , COVID-19 , RNA, Long Noncoding , Autism Spectrum Disorder/therapy , Child , Humans , Kidney , SARS-CoV-2
13.
Med Hypotheses ; 167: 110948, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2031564

ABSTRACT

Finding effective drugs to treat SARS-CoV-2 infection as a complementary step to the extensive vaccination is of the great importance to overcome the current pandemic situation. It has been shown that some bio-active unsaturated fatty acids such as Arachidonic Acid (AA) can reduce the infection severity and even destroy the virus by disintegration of the virus lipid envelope. On the other hand, it has been reported that several designed peptides with an activity similar to the angiotensin converting enzyme 2 (ACE-2), which has a high affinity towards the novel corona virus spike protein, can inhibit the viral infection through concealing the spike proteins from the cell surfaces ACE-2. Binding the mentioned peptides to the bio-active lipids like AA will result in a lipopeptide surfactant molecule with the synergistic effect of both the active moieties in its structure to treat the novel corona infection. In addition, the peptide segment increases the aqueous solubility of the lipid segment and enables the targeted delivery of the surfactant molecule to the virus. The resultant lipopeptide would be a potentially effective drug for SARS-CoV-2 infection treatment with the minimum side effects.

14.
Bulletin of Siberian Medicine ; 21(2):195-206, 2022.
Article in English | Scopus | ID: covidwho-2026053

ABSTRACT

An immune response to invasion of viral pathogens is an integral part of maintaining the physiological functioning of the bronchopulmonary system and effective gas exchange. Collagen-containing C-type lectins (lung collectins) are some of the key proteins in the identification of viral particles. They have image-recognizing receptors that identify pathogen-associated molecular patterns, particularly viral glycoproteins. The surfactant proteins SP-A and SP-D, which are composed of trimerized units, belong to pulmonary collectins and oligomerize into higher-order structures. These proteins play an essential role in recognition and elimination of microbial pathogens (viruses, bacteria, fungi, parasites, nanoparticles, allergens) through a variety of mechanisms. Taking into account the burden of the novel coronavirus infection caused by the SARS-CoV-2 virus, it is important to consider the role of the surfactant proteins SP-A and SP-D in the pathogenesis of the immune response to viral invasion. Currently, there are data on the direct relationship between surfactant proteins and viruses belonging to the Coronaviridae family. The SP-A and SP-D proteins modulate inflammatory responses and cytokine synthesis, but prevent an excessive inflammatory response (cytokine storm). There is also an assumption that SARSCoV-2 directly suppresses and alters the production of surfactant proteins. Thus, the key pathogenetic role of the surfactant proteins SP-A and SP-D in the response to the viral pathogen SARS-CoV-2 is evident. Today, this is a promising area of translational medicine, which will contribute to a profound understanding of the pathogenesis of coronavirus infection for assessing the diagnostic and prognostic potentials of the surfactant proteins SP-A and SP-D in COVID-19. Additionally, it will help evaluate the therapeutic potential of recombinant fragments of human SP-A and SP-D. © 2022 Siberian State Medical University. All rights reserved.

15.
Molecules ; 27(17)2022 Aug 25.
Article in English | MEDLINE | ID: covidwho-2023942

ABSTRACT

Liquid soaps are the basic cosmetics used to clean the skin of the hands. Frequent hand washing prevents viral contamination but may damage the skin's hydro-lipid layer, leading to various types of irritation. Therefore, four liquid soap formulas were developed with three amphoteric surfactants: Cocamidopropyl Betaine (LS II), CocamidopropylHydroxysultaine (LS III), and newly synthesized Evening PrimroseaamidopropylSulfobetaine (LS IV). We evaluated the skin irritating potential (zein number, bovine albumin test) and cytotoxicity (AlamarBlue™, Cell viability, and Cell cycle assays) on HaCaT cell line. We observed lower values of the zein number and bovine albumin tests after adding soaps with surfactants (the highest differences in LS IV) compared to the base soap (LS I). However, LS I and LS II did not differ in cytotoxic assays. Therefore, adding LS III and LS IV seems potentially more dangerous to the cells. However, it should be noted that cells were continuously exposed to liquid soaps for more than 24 h, so its cytotoxic effects after dermal use in humans may be unnoticeable. Concluding, results suggest that the newly synthesized LS IV should improve the safety of liquid hand washing soaps.


Subject(s)
Soaps , Zein , Animals , Cattle , Hand Disinfection/methods , Humans , Serum Albumin, Bovine , Soaps/pharmacology , Surface-Active Agents/pharmacology
16.
Her Russ Acad Sci ; 92(4): 404-411, 2022.
Article in English | MEDLINE | ID: covidwho-2008772

ABSTRACT

COVID-19 is characterized by a severe course in approximately 5‒10% of patients, who require admittance to the intensive care unit and mechanical ventilation, which is associated with a very high risk of a poor prognosis. At present, in real clinical practice, in managing severe patients with COVID-19, noninvasive ventilation (NIV) is widely used (in some countries, up to 60% of all methods of respiratory support). In most studies on the effectiveness of NIV in hypoxemic acute respiratory failure in patients with COVID-19, the need for tracheal intubation and hospital mortality with the use of NIV averaged 20-30%, which suggests the rather high efficiency of this method. The COVID-19 pandemic has given a powerful impetus to the widespread use of prone positioning among nonintubated patients with acute respiratory failure caused by COVID-19. Several studies have shown that prone positioning can reduce the need for mechanical ventilation and hospital mortality. Medications that have proven effective in severe forms of COVID-19 include remdesivir, systemic glucocorticoids, tocilizumab, baricitinib, and anticoagulants. Among the new promising areas of drug therapy, noteworthy is the use of thiol-containing drugs (N-acetylcysteine), inhaled surfactant, and inhaled prostacyclin analogues.

17.
Comput Struct Biotechnol J ; 20: 4984-5000, 2022.
Article in English | MEDLINE | ID: covidwho-2007640

ABSTRACT

Surfactant protein D (SP-D) is an essential component of the human pulmonary surfactant system, which is crucial in the innate immune response against glycan-containing pathogens, including Influenza A viruses (IAV) and SARS-CoV-2. Previous studies have shown that wild-type (WT) SP-D can bind IAV but exhibits poor antiviral activities. However, a double mutant (DM) SP-D consisting of two point mutations (Asp325Ala and Arg343Val) inhibits IAV more potently. Presently, the structural mechanisms behind the point mutations' effects on SP-D's binding affinity with viral surface glycans are not fully understood. Here we use microsecond-scale, full-atomistic molecular dynamics (MD) simulations to understand the molecular mechanism of mutation-induced SP-D's higher antiviral activity. We find that the Asp325Ala mutation promotes a trimannose conformational change to a more stable state. Arg343Val increases the binding with trimannose by increasing the hydrogen bonding interaction with Glu333. Free energy perturbation (FEP) binding free energy calculations indicate that the Arg343Val mutation contributes more to the increase of SP-D's binding affinity with trimannose than Asp325Ala. This study provides a molecular-level exploration of how the two mutations increase SP-D binding affinity with trimannose, which is vital for further developing preventative strategies for related diseases.

18.
International Journal of Applied Pharmaceutics ; 14(4):279-281, 2022.
Article in English | EMBASE | ID: covidwho-1998137

ABSTRACT

Objective: Development of micelle mediated cloud point extraction (CPE) and preconcentration of aurintricarboxylic acid (ATCA) (a viral inhibitor). Methods: The method is based on the ion-pair formation between ATCA and a cationic surfactant tetrabutylammonium bromide (TBAB), which is extracted into the Triton X-114 (TX-114, a non-ionic surfactant) at a pH 4.4. The effect of different important parameters like pH, the concentration of surfactants (TX-114 and TBAB), salt, temperature, and time for the extraction of ATCA was optimized. Results: Extraction efficiency of 90.28 % for CPE of ATCA was obtained using mixed micelles of TX-114 and TBAB. The linear range and limits of detection for ATCA was found to be 8.44-84.47 µg ml-1 and 8.14 ng ml-1, respectively. Conclusion: The suggested CPE method has been applied to the determination of ATCA in aqueous solutions.

19.
Journal of Hepatology ; 77:S691-S692, 2022.
Article in English | EMBASE | ID: covidwho-1996646

ABSTRACT

Background and aims: Acute respiratory distress syndrome (ARDS) is a serious complication of COVID-19 and present in a large percentage of COVID-19 deaths. Many studies suggest that people with obesity are at increased risk of severe COVID-19, however, mechanism on liver-lung axis remains unknown. We aimed to evaluate whether bile acid (BAs) trafficking interfere with acute lung injury (ALI) in animal model with obesity. Method: Leptin deficient (ob/ob) mice fed with high-fat-diet (Ob/Ob HFD) were i.p injected with oleic acid (OA) to induce ALI. To modulate BAs uptake, mice were i.p treated with neutralizing antibody for sodium taurocholate co-transporting polypeptide (NTCP;BAs-transporter). Broncho-alveolar lavage fluid (BALF), lungs, livers and serum were obtained from mice and assessed for inflammatory (HandE staining, ALT and pro-inflammatory panel of cytokines), fibrosis (Sirius red staining, a-smooth muscle actin, collagen and fibronectin) and metabolic (BAs, cholesterol, triglyceride, glucose tolerance test (GTT) and fasting blood sugar (FBS)) profiles. In addition, alveolarcapillary membrane injury of surfactant D (SP-D) and the receptor for advanced glycation end-products (RAGE). BAs trafficking were assessed in primary lung cells and their impact on proliferation and apoptosis were evaluated. Results: Compared to WT-littermates, OA-induced lung injury and was worsened in the in the Ob/Ob HFD in the histopathology outcome. In addition, BALF of the Ob/Ob HFD showed elevated levels of BAs (3- fold;P = 0.002) associated with increased GM-CSF, INF-g, IL-1, IL-6 and IL-8 (p < 0.01). Moreover, Ob/Ob HFD with OA showed elevated serum levels in liver enzymes, lipids, glucose and metabolic markers (p < 0.01). In addition, Ob/Ob HFD livers showed an exacerbated fibrosis profile. NTCP neutralizing antibody in Ob/Ob HFD while inhibited BAs uptake/trafficking in both primary alveolar type II (BALF showed 4-fold increase in BAs) and primary hepatocytes (serum showed 3-fold increase in BAs). SP-D, RAGE and serum metabolic markers were suppressed to normal in line with enhance lung and liver histology and maintaining cell viability. Conclusion: Modulation of BAs trafficking from the liver of obese mice to the lungs could be an important step in the pathogenesis of ALI. Antagonizing BAs uptake may suggest a therapeutic strategy in improving liver-lung axis.

20.
Pediatr Neonatol ; 63(4): 341-347, 2022 07.
Article in English | MEDLINE | ID: covidwho-1977713

ABSTRACT

Respiratory distress syndrome (RDS) is the major cause of respiratory failure in preterm infants due to immature lung development and surfactant deficiency. Although the concepts and methods of managing respiratory problems in neonates have changed continuously, determining appropriate respiratory treatment with minimal ventilation-induced lung injury and complications is crucially important. This review summarizes neonatal respiratory therapy's advances and available strategies (i.e., exogenous surfactant therapy, noninvasive ventilation, and different ventilation modes), focusing on RDS management.


Subject(s)
Interactive Ventilatory Support , Noninvasive Ventilation , Respiratory Distress Syndrome, Newborn , Humans , Infant , Infant, Newborn , Infant, Premature , Respiratory Distress Syndrome, Newborn/therapy , Surface-Active Agents
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