Chronic obstructive pulmonary disease (COPD) is a multifactorial disease of the respiratory system that affects the lung parenchyma and airways; it is one of the leading causes of death in the world, which explains the constant search for new approaches to diagnosis, treatment and prevention of the disease. COPD develops as a result of a complex interaction of molecular genetic factors, a network of epigenetic regulators, and environmental factors that are closely related to lifestyle. The molecular pathogenesis of COPD may include the mechanisms of alteration of the regulation of stressful reactions that prevent cellular senescence. Non-coding RNAs play an important role in the regulation of various intracellular signaling pathways and is the most relevant subject of genetic studies of various pathological phenotypes. The expression profile of long non-coding RNA is often disregulated in various diseases. Information on the role of long non-coding RNA in the development of COPD is limited. Long non-coding RNA and the target-genes of signaling pathways involved in cellular senescence form a complex interactive network and may be targets for disease therapy. The review presents the data concerning some aspects of the molecular pathogenesis of COPD, as well as role of long non-coding RNAs in the development of the COPD.

Background/Objectives: Chronic obstructive pulmonary disease (COPD) is increasingly viewed as a disorder of impaired cellular adaptation to chronic stress, involving oxidative injury, mitochondrial dysfunction, and accelerated cellular senescence. We investigated whether genetic variation in these pathways contributes to disease susceptibility, lung function impairment, and polygenic risk prediction. Methods: Thirty-three single-nucleotide variants were analysed in 747 patients with COPD and 703 controls. Associations with disease susceptibility and lung function parameters were assessed using regression models with correction for multiple testing. Weighted and unweighted polygenic scores were constructed from associated variants and evaluated using receiver operating characteristic and net reclassification improvement analyses. Results: Significant associations were identified in genes involved in antioxidant defence (NFE2L2, HMOX1, GSR), PI3K/AKT/mTOR signalling (PIK3R1, PTEN), mitochondrial function (TOMM40), cellular stress responses (FOXO3A), and long non-coding RNA regulation (MEG3, CDKN2B-AS1). The strongest association was observed for PIK3R1 rs831125 (OR = 2.31, p = 2.53 × 10⁻¹⁰). Variants in NFE2L2, PIK3R1, MEG3, MALAT1, and SIRT3 were additionally associated with pulmonary function parameters. The weighted polygenic score demonstrated good discriminative ability (AUC 68.8%, 95% CI 65.9–71.7%) and substantially improved prediction when combined with age, sex, and smoking exposure (AUC 88.1%, 95% CI 86.3–89.8%; NRI = 0.62, p = 2.21 × 10⁻²⁸). Conclusions: The identified loci converge on interconnected pathways involved in cellular stress adaptation, mitochondrial homeostasis, and senescence, supporting their contribution to chronic obstructive pulmonary disease susceptibility and functional decline.

Introduction. Idiopathic pulmonary fibrosis (IPF) comprises an interstitial lung disease with unclear pathogenesis, rapid progression, and no effective treatment. Pulmonary fibrosis is reported to be one of the most severe complications induced by a new coronavirus infection COVID-19. The mechanisms triggering pulmonary fibrosis and leading to its rapid progression remain substantially unclear. Evidence suggests that immune and genetic factors contribute to the development of this disease. Among the latter, the role of long non-coding RNAs (dnRNAs) has been actively studied to date. Materials and methods. Considering the role of TP53TG1, LINC00342, H19, MALAT1, DNM3OS, and MEG3 dnRNAs as regulators of signaling pathways associated with fibroblast activation and epithelial-mesenchymal transition, the authors analyzed the expression level of selected dnRNAs in lung tissue and blood mononuclear cells of patients with IPF (N = 12), post-COVID-19 pulmonary fibrosis (N = 14), and in control group (N = 27). Results and discussion. Blood mononuclear cells in patients with IPF and post-COVID-19 PF revealed similar patterns of TP53TG1 and MALAT1 dnRNA expression. The level of relative expression of MALAT1 was significantly higher in patients with IPF (Fold Change=3.207, P = 0.0005) and with post-COVID-19 PF (Fold Change=9.854, P = 0.0003), while the relative expression level of TP53TG1 reduced in patients with IPF (Fold Change=0.4308, P = 0.0313) and with post-COVID-19 PF (Fold Change=0.1888, P = 0.0003 in blood mononuclear cells, Fold Change=0.1791, P = 0.0237 in lung tissue). Increased expression of DNM3OS in blood mononuclear cells (Fold Change=12.899, P = 0.0016) and lung tissue (Fold Change=9.527, P = 0.0001), LINC00342 (Fold Change=2.221, P = 0.0309) in blood mononuclear cells was revealed only in patients with IPF. Conclusion. Evaluation of the dnRNA expression profile of TP53TG1, LINC00342, MALAT1 and DNM3OS in blood mononuclei can be used as an informative and non-invasive biomarker in IPF and post COVID-19 PF.

Idiopathic pulmonary fibrosis (IPF) is the most common form of fibrosis of internal organs. The etiology and pathogenesis of IPF are still not well understood. However, a growing line of evidence shows that both genetic and non-genetic factors contribute to IPF development. The release of pro-inflammatory cytokines activates the immune cells. The enhanced synthesis of interleukins and cytokines, especially transforming growth factor β1 leads to the proliferation of fibroblasts, increased extracellular matrix formation, and epithelial-mesenchymal transformation of the lung tissue. These pathological changes could lead to fibrosis. Polymorphisms of genes responsible for the function of mucociliary clearance (MUC5B), telomerases (TERT, TERC), as well as signaling pathway related-genes such as Sonic hedgehog, Wnt, and some other genes are also risk factors for IPF development. Epigenetic regulatory mechanisms, such as methylation and acetylation of DNA and histones, may also influence the development and progression of this disease. At present, the role of non-coding RNAs, in particular long non-coding RNAs (lncRNA) in the development of fibrotic processes, is actively studied. LncRNA is an RNA that is longer than 200 base pairs and does not code for any proteins. LncRNAs perform various functions in the cell, from nuclear compartmentation to epigenetic regulation of gene expression and post-translational modification of proteins. In this review, we present the important aspects in the pathogenesis of IPF.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease of unknown origin with an average life expectancy of 3-5 years after diagnosis. The disease is accompanied by progressive pulmonary fibrosis, decreased lung function, poor response to therapy and early mortality. Various biomarkers, including serum biomarkers, are used for timely and differential diagnosis of idiopathic pulmonary fibrosis (IPF) and COVID-19-associated pulmonary fibrosis (PF), predicting the course of the disease and assessing the effectiveness of specific therapy. Target was to investigate the features of pulmonary fibrosis based on serum biomarkers in patients with ILF and COVID-19-associated fibrosis. Methods. Changes in serum concentrations of biomarkers CA15-3, LOXL2, TGFBR3 and periostin in patients with ILF (n=10), COVID-19-associated pulmonary fibrosis and controls were investigated. Results. Significant differences were found between LOXL2 concentrations in the control and ILF groups (p=0.003), ILF and COVID-19-associated fibrosis groups (p=0.036) and between periostin concentrations in the control and ILF groups (p=0.042). ROC analysis for LOXL2 revealed: in the ILF and control groups AUC=0.854 (95% CI 0.693-1.0; p<0.0001), with a sensitivity of 80.0% and specificity of 76.9%; in the ILF and COVID-19-associated LF groups AUC=0.773 (95% CI 0.556-0.989; p=0.014) with a sensitivity of 99.0% and specificity of 63.6%. For periostin: AUC=0.692 (95% CI 0.469-0.916; p=0.092) with a sensitivity of 50.0% and specificity of 84.6%. Correlation analysis in the pooled group showed a significant correlation for CA15-3 and periostin (rs=0.383; 95% CI 0.042-0.645; p=0.025), LOXL2 and periostin (rs=0.509; 95% CI 0.196-0.727; p=0.002), TGFBR3 and CA15-3 (rs=0.347; 95% CI 0.0-0.62; p=0.044). Conclusions. We found significant differences between serum levels of LOXL2 in ILF group and CG, ILF group and COVID-19-associated LF. ROC analysis yielded the values of the optimal points of group separation by serum LOXL2 and periostin levels. This allows differential diagnosis of different pulmonary fibrosis. Keywords: pulmonary fibrosis, IPF, COVID-19, CA15-3, periostin, TGFBR3, LOXL2.