The review presents an analysis of scientific publications in recent years devoted to the study on the cellular-molecular mechanism of cellular adaptation to hypoxia. In many respiratory diseases (chronic obstructive pulmonary disease, chronic respiratory failure, etc.), the balance between the cells’ need for oxygen and its delivery is disrupted. It complicates the course of the diseases and is a potential factor in their progression. The microenvironment in the inflammatory areas becomes hypoxic (so-called inflammatory hypoxia). The formation of long-term adaptation to pathological hypoxia is associated with the expression of a specific hypoxia-induced factor (HIF). It serves as a transcription activator for more than 300 genes and is a key regulator of various cellular and systemic responses to hypoxia, including angiogenesis, cell proliferation, cellular migration, regeneration, antigen presentation, cytokine and antimicrobial peptide production, phagocytosis, apoptosis, and cellular metabolic reprogramming. The article also considers the complex cross-interaction between HIF signaling and the nuclear transcription factor κB — NF-κB) signaling pathway (one of the main regulators of inflammation and immune responses). Possible therapeutic methods for controlling inflammation and immune-related diseases based on the principle of regulating the HIF signaling pathway are discussed. KEYWORDS: respiratory diseases, hypoxia, hypoxia-induced factor, adaptation, inflammation, immunity, targeted therapy. FOR CITATION: Titova O.N., Kuzubova N.A., Lebedeva E.S. The role of the hypoxia signaling pathway in cellular adaptation to hypoxia. Russian Medical Inquiry. 2020;4(4):207–213. DOI: 10.32364/2587-6821-2020-4-4-207-213.
Background: the majority of patients who experienced COVID-19, lung disorders persist for a long term. It remains unclear how reversible they are and what the clinical and radiation predictors of these changes are. Aim: to determine the consequences of pneumonia caused by the SARS-CoV-2 virus in patients who experienced COVID-19 during the period of 2020–2021; to evaluate possible clinical and radiation predictors of these changes and their reversibility. Patients and Methods: the article presents the analyzed results of radiation studies (computed tomography (CT), single-photon emission computed tomography (SPECT)), spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO) performed in 68 patients who had COVID-19 during the period of 2020–2021 and complained of persistent shortness of breath, fatigue and disability. Results: 1–2 years after, there was a decrease in the bronchial patency to 39.2±4.5%pred in 63% of patients with mild COVID-19, which correlated (rs>0.92) with a decrease in microcirculation (MC) over 50% and mosaic attenuation (rs>0.77), air trapping (rs>0.89) and bronchiolectasis (rs>0.64). In mixed ventilatory defects (MEF75 to 46.8±3.6% of predicted, DLCO 62.4±3.1% of predicted), there were significant MC disorders over 70%, corresponding to zones of focal pneumosclerosis (rs>0.93). In the severe disease course, single areas of "frosted glass" were detected in 13% of patients, while mosaic attenuation and air trapping were detected in 34%, which was accompanied by a decrease in MEF75 to 37.4±3.7% of predicted. During a decrease in DLCO to 52.4±2.2% of predicted, there were a compaction of the interstitial by the type of usual interstitial pneumonia of small extent (65%), consolidation areas (34%), pneumosclerosis areas (54%), platelike atelectasis (31%), bronchiectasis (26%), signs of bronchiolitis obliterans (42%), and pulmonary hypertension development (38%). According to the single- photon emission computed tomography data, there were significant disorders of the MC. Irreversible changes were detected in lung areas with an inadequate perfusion of more than 50%, observed 6 months after the disease, and subsequently, after 1 year or more. Conclusions: a comprehensive functional lung imaging in radiation therapy increases the efficacy of clinical examination of patients in the postcovid period. The following type of patients need a comprehensive radiation monitoring: patients over 60 y.o., patients who had a severe COVID-19; patients who have respiratory complaints over 1 year, regardless of the COVID-19 severity. Microcirculation disorders over 50% detected 6 months after the disease are a predictor of changes in the lung parenchyma and may indicate long-term disease consequences. KEYWORDS: postcovid syndrome, microcirculation, computed tomography of the lungs, ventilation, artificial intelligence. FOR CITATION: Zolotnitskaya V.P., Speranskaya A.A., Kuzubova N.A. et al. Long-term effects of COVID-19 in patients according to the functional lung imaging in radiation therapy. Russian Medical Inquiry. 2022;6(7):360–366 (in Russ.). DOI: 10.32364/2587-6821- 2022-6-7-360-366.
Aim: to evaluate the effect of pulmonary surfactant therapy in the complex treatment of severe community-acquired pneumonia caused by the SARS-CoV-2 on the disease course and outcome and to determine the possibility of using the level of surfactant protein D (surfactant protein D, SP-D) in blood serum as a criterion for the treatment efficacy. Patients and Methods: a prospective randomized study included 60 patients. Inclusion criteria confirmed SARS-CoV-2; bilateral pneumonia with at least grade 3 of lesion according to CT; SpO2 less than 92%. Patients were divided into two groups: group 1 (n=30) received surfactant therapy in addition to standard therapy, group 2 (n=30) received only standard therapy. Surfactant was administered by inhalation at a dose of 150–300 mg/day. The duration of surfactant therapy was 10 days. Arterial blood gas values, clinical parameters and SP-D levels were analyzed before and after treatment. Results: 48 hours after the therapy start, a statistically significant increase in SpO2 was registered in patients from group 1 versus an increase in patients from group 2 (p=0.048). On the 10th day of treatment, group 1 versus group 2 showed a statistically significant increase in the oxygenation index (PaO2/FiO2) (266.82±10.5 mmHg vs. 199.67±11.7 mmHg, respectively, p=0.001), a decrease in the frequency of artificial lung ventilation (ALV) (27% vs. 67%, respectively, p=0.002), length of hospital stay (21.0 (15;25) days vs. 27.0 (15;35) days, respectively, p=0.05). The fatal outcome was registered in 8 (27%) patients from group 1 and 18 (60%) patients from group 2 (p=0.001). Among patients from group 1 who had a favorable disease outcome, in 84% of cases surfactant therapy was prescribed in a shorter period from the disease onset versus patients whose treatment was ineffective (3±1.5 days vs. 7±2.0 days). A stable, reliable correlation was established between SP-D and PaO2 (r= 420, p=0.001), between SP-D and PaO2/FiO2 (r=460, p=0.001). Conclusion: the major effects of surfactant therapy are a faster recovery of the arterial blood gas, a decrease in the frequency of ALV, the length of hospital stay, and mortality. The success of surfactant therapy is associated with its early prescription. Surfactant therapy can be considered as an additional pathogenetically justified component in the complex treatment of severe pneumonia caused by the SARS-CoV-2. Significantly higher levels of SP-D were observed in patients with severe pneumonia associated with COVID-19, with the disease progression and adverse outcome. KEYWORDS: SARS-CoV-2, COVID-19, pneumonia, surfactant, artificial lung ventilation, respiratory failure, surfactant protein D, SP-D. FOR CITATION: Volchkova E.V., Alexandrovich Yu.S., Titova O.N. et al. Pulmonary surfactant in the complex treatment of severe pneumonia associated with COVID-19. Efficacy markers. Russian Medical Inquiry. 2022;6(7):352–359 (in Russ.). DOI: 10.32364/2587-6821-2022-6-7-352-359.
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