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1.
Respir Physiol Neurobiol ; 294: 103767, 2021 12.
Article in English | MEDLINE | ID: covidwho-1330032

ABSTRACT

A computational model of the transport of gases involved in spontaneous breathing, from the trachea inlet to the alveoli was developed for healthy patients. Convective and diffusive transport mechanisms were considered simultaneously, using a diffusion coefficient (D) that has considered the four main species of gases present in the exchange carried out by the human lung, nitrogen (N2), oxygen (O2), carbon dioxide (CO2) and water vapor (H2O). A Matlab® script was programmed to simulate the trachea-alveolus gas exchange model under three respiratory frequencies: 12, 24 and 40 breaths per minute (BPM), each with three diaphragmatic movements of 2 cm, 4 cm, and 6 cm. During the simulations, the CO2 inlet concentrations in the alveoli and the O2 concentration at the inlet of the trachea were kept constant. A simplified but stable model of mass transport between the trachea and alveoli was obtained, allowing the concentrations to be determined dynamically at the selected test points in the airway.


Subject(s)
Models, Theoretical , Pulmonary Alveoli/physiology , Pulmonary Gas Exchange/physiology , Respiration , Trachea/physiology , Humans
2.
Proc Natl Acad Sci U S A ; 118(19)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1214016

ABSTRACT

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.


Subject(s)
Lab-On-A-Chip Devices , Models, Biological , Pulmonary Alveoli/physiology , Alveolar Epithelial Cells , Antiviral Agents/pharmacology , Cigarette Smoking/adverse effects , Dimethylpolysiloxanes/chemistry , Gelatin/chemistry , Humans , Hydrogels/chemistry , Methacrylates/chemistry , Porosity , Pulmonary Alveoli/cytology , Pulmonary Alveoli/pathology , Respiration , Respiratory Mucosa/cytology , Respiratory Mucosa/physiology , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity
3.
Crit Care ; 25(1): 81, 2021 02 24.
Article in English | MEDLINE | ID: covidwho-1102346

ABSTRACT

BACKGROUND: There is a paucity of data concerning the optimal ventilator management in patients with COVID-19 pneumonia; particularly, the optimal levels of positive-end expiratory pressure (PEEP) are unknown. We aimed to investigate the effects of two levels of PEEP on alveolar recruitment in critically ill patients with severe COVID-19 pneumonia. METHODS: A single-center cohort study was conducted in a 39-bed intensive care unit at a university-affiliated hospital in Genoa, Italy. Chest computed tomography (CT) was performed to quantify aeration at 8 and 16 cmH2O PEEP. The primary endpoint was the amount of alveolar recruitment, defined as the change in the non-aerated compartment at the two PEEP levels on CT scan. RESULTS: Forty-two patients were included in this analysis. Alveolar recruitment was median [interquartile range] 2.7 [0.7-4.5] % of lung weight and was not associated with excess lung weight, PaO2/FiO2 ratio, respiratory system compliance, inflammatory and thrombophilia markers. Patients in the upper quartile of recruitment (recruiters), compared to non-recruiters, had comparable clinical characteristics, lung weight and gas volume. Alveolar recruitment was not different in patients with lower versus higher respiratory system compliance. In a subgroup of 20 patients with available gas exchange data, increasing PEEP decreased respiratory system compliance (median difference, MD - 9 ml/cmH2O, 95% CI from - 12 to - 6 ml/cmH2O, p < 0.001) and the ventilatory ratio (MD - 0.1, 95% CI from - 0.3 to - 0.1, p = 0.003), increased PaO2 with FiO2 = 0.5 (MD 24 mmHg, 95% CI from 12 to 51 mmHg, p < 0.001), but did not change PaO2 with FiO2 = 1.0 (MD 7 mmHg, 95% CI from - 12 to 49 mmHg, p = 0.313). Moreover, alveolar recruitment was not correlated with improvement of oxygenation or venous admixture. CONCLUSIONS: In patients with severe COVID-19 pneumonia, higher PEEP resulted in limited alveolar recruitment. These findings suggest limiting PEEP strictly to the values necessary to maintain oxygenation, thus avoiding the use of higher PEEP levels.


Subject(s)
COVID-19/complications , Pneumonia, Viral/therapy , Positive-Pressure Respiration , Pulmonary Alveoli/physiology , Aged , COVID-19/diagnostic imaging , COVID-19/epidemiology , COVID-19/physiopathology , Cohort Studies , Female , Humans , Italy/epidemiology , Male , Middle Aged , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/virology , Pulmonary Alveoli/diagnostic imaging , Severity of Illness Index , Tomography, X-Ray Computed , Treatment Outcome
4.
Am J Physiol Cell Physiol ; 319(6): C991-C996, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-751459

ABSTRACT

Alveoli are the gas-exchanging units of the lung, and the alveolar barrier is often a key battleground where pathogens, allergens, and other insults from the environment are encountered. This is seen in the current coronavirus disease 2019 (COVID-19) pandemic, as alveolar epithelium is one of the major targets of SARS-COV-2, the virus that causes COVID-19. Thus, it is essential to understand the mechanisms in order to maintain the integrity of alveoli epithelium. Alveolar type II (AT2) cells behave as tissue stem cells that repair alveoli epithelium during steady-state replacement and after injury. However, not all AT2 cells are equal in their ability for self-renewal or differentiation. Through marker gene identification, lineage tracing, and single-cell RNA-sequencing (scRNA-seq), distinct subpopulations of AT2 cells have been identified that play the progenitor role in a different context. The revelation of AT2 heterogeneity has brought new insights into the role of AT2 cells in various lung disease settings and potentiates the finding of more therapeutics targets. In this mini review, we discuss the recently identified subpopulations of AT2 cells and their functions under steady-state, postinjury, and pathological conditions.


Subject(s)
COVID-19/pathology , Homeostasis/physiology , Pulmonary Alveoli/cytology , Pulmonary Alveoli/physiology , SARS-CoV-2 , Animals , Humans , Pulmonary Alveoli/pathology
5.
Eur Rev Med Pharmacol Sci ; 24(16): 8585-8591, 2020 08.
Article in English | MEDLINE | ID: covidwho-745634

ABSTRACT

Some surface proteins of the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can bind to the hemoglobin molecule of an erythrocyte, which leads to the destruction of the structure of the heme and the release of harmful iron ions to the bloodstream. The degradation of hemoglobin results in the impairment of oxygen-carrying capacity of the blood, and the accumulation of free iron enhances the production of reactive oxygen species. Both events can lead to the development of oxidative stress. In this case, oxidative damage to the lungs leads then to the injuries of all other tissues and organs. The use of uridine, which preserves the structure of pulmonary alveoli and the air-blood barrier of the lungs in the course of experimental severe hypoxia, and dihydroquercetin, an effective free radical scavenger, is promising for the treatment of COVID-19. These drugs can also be used for the recovery of the body after the severe disease.


Subject(s)
Coronavirus Infections/pathology , Oxidative Stress , Pneumonia, Viral/pathology , Betacoronavirus , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Cytokines/metabolism , Erythrocytes/cytology , Erythrocytes/metabolism , Erythrocytes/virology , Free Radical Scavengers/pharmacology , Free Radical Scavengers/therapeutic use , Hemoglobins/metabolism , Humans , Oxidative Stress/drug effects , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Pulmonary Alveoli/drug effects , Pulmonary Alveoli/physiology , Quercetin/analogs & derivatives , Quercetin/pharmacology , Quercetin/therapeutic use , Reactive Oxygen Species/metabolism , SARS-CoV-2 , Uridine/pharmacology , Uridine/therapeutic use
6.
J Int Med Res ; 48(7): 300060520939746, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-690568

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 infection is a serious global concern. Increased morbidity and mortality is associated with older age, male gender, cardiovascular disease, diabetes, and smoking. As COVID-19 spreads from coastal borders, both state to state and country to country, our understanding of its pathophysiology has evolved. Age and type 2 diabetes mellitus (T2DM) play especially important roles in COVID-19 progression. T2DM is an age-related disease associated with metabolic syndrome, obesity, insulin resistance (hyperinsulinemia), hyperlipidemia, hypertension, hyperglycemia, and endothelial activation and dysfunction. This review evaluates the relationships and intersection between endothelial cell activation and dysfunction in T2DM and COVID-19. COVID-19 induces multiple injuries of the terminal bronchioles and alveolar blood-gas barrier and associated ultrastructural tissue remodeling. COVID-19 may unmask multiple vulnerabilities associated with T2DM including damage to the endothelial glycocalyx and multiple end-organ macro and microvascular diseases. Unmasking existing vulnerabilities in diabetic patients with COVID-19 is important. Globally, we must come together to better understand why T2DM is associated with increased COVID-19 morbidity and mortality.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/physiopathology , Endothelial Cells/physiology , Metabolic Syndrome/complications , Metabolic Syndrome/physiopathology , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , Animals , Blood-Air Barrier/pathology , Blood-Air Barrier/physiopathology , Bronchioles/pathology , Bronchioles/physiopathology , COVID-19 , Comorbidity , Coronavirus Infections/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Drug Repositioning , Endothelial Cells/pathology , Humans , Metabolic Syndrome/epidemiology , Models, Biological , Pandemics , Pneumonia, Viral/epidemiology , Pulmonary Alveoli/physiology , Pulmonary Alveoli/physiopathology , Rats , SARS-CoV-2 , Wound Healing/physiology
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