Development of fibrosis and impairment of lung function in patients with a new coronavirus disease

The aim: review scientific research to find out whether the new coronavirus infection (NCI) causes fibrotic changes in the lungs and, if any, how long they persist and whether functional disorders of the respiratory system accompany them. Disruption of the functional state of the lungs in patients with severe novel coronavirus disease (COVID-19) is still seen 6 months after completion of inpatient treatment. High-resolution computed tomography (HRCT) demonstrates persistent pathological changes in the lungs, some of which are fibrosis-like. Pathomorphological features of the COVID-19 course, as well as the ability of the virus to activate connective tissue growth factor (CTGF) and enhance the signaling of transforming growth factor-beta (TGF-β), can contribute to lung tissue fibrosis. Increased titers of antinuclear autoantibodies and specific autoantibodies indirectly reveal dysregulation of the immune response leading to the progression of organizing pneumonia and fibrotic changes in the lung tissue. These increased titers can also indicate the need to prescribe immunosuppressive and antifibrotic drugs. Researchers are considering the possibility of including antifibrotic drugs in combination therapy for severe COVID-19 in the early stages of treatment in patients with risk factors for developing pulmonary fibrosis. However, further monitoring and determination of the role of antifibrotic drugs are required. Sometimes patients with COVID-19 develop severe, irreversible fibrotic lung disease, and lung transplantation is the only treatment option.Conclusion. There is no unequivocal opinion among researchers concerning the clinical significance and further prognosis of COVID-19 so far, which is a reason for further studies.

Pirfenidone vs. nintedanib in patients with idiopathic pulmonary fibrosis: a retrospective cohort study

Background Two antifibrotic drugs, pirfenidone and nintedanib, are licensed for the treatment of patients with idiopathic pulmonary fibrosis (IPF). However, there is neither evidence from prospective data nor a guideline recommendation, which drug should be preferred over the other. This study aimed to compare pirfenidone and nintedanib-treated patients regarding all-cause mortality, all-cause and respiratory-related hospitalizations, and overall as well as respiratory-related health care costs borne by the Statutory Health Insurance (SHI). Methods A retrospective cohort study with SHI data was performed, including IPF patients treated either with pirfenidone or nintedanib. Stabilized inverse probability of treatment weighting (IPTW) based on propensity scores was applied to adjust for observed covariates. Weighted Cox models were estimated to analyze mortality and hospitalization. Weighted cost differences with bootstrapped 95% confidence intervals (CI) were applied for cost analysis. Results We compared 840 patients treated with pirfenidone and 713 patients treated with nintedanib. Both groups were similar regarding two-year all-cause mortality (HR: 0.90 95% CI: 0.76; 1.07), one-year all cause (HR: 1.09, 95% CI: 0.95; 1.25) and respiratory-related hospitalization (HR: 0.89, 95% CI: 0.72; 1.08). No significant differences were observed regarding total (€− 807, 95% CI: €− 2977; €1220) and respiratory-related (€− 1282, 95% CI: €− 3423; €534) costs. Conclusion Our analyses suggest that the patient-related outcomes mortality, hospitalization, and costs do not differ between the two currently available antifibrotic drugs pirfenidone and nintedanib. Hence, the decision on treatment with pirfenidone versus treatment with nintedanib ought to be made case-by-case taking clinical characteristics, comorbidities, comedications, individual risk of side effects, and patients’ preferences into account.

Efficacy of early antifibrotic treatment for idiopathic pulmonary fibrosis

Background Although antifibrotic drugs, including nintedanib and pirfenidone, slow the progression of idiopathic pulmonary fibrosis (IPF), there is little data about the timing of start of antifibrotic treatment in real-world clinical practice. The present study aimed to clarify the efficacy of nintedanib and pirfenidone in patients with early-stage IPF. Methods We compared survival and disease progression between patients with IPF with Japanese Respiratory Society (JRS) disease severity system stage I with and without oxygen desaturation on the 6-min walk test (6MWT) and increased the gender–age–physiology (GAP) staging. We examined the efficacy of antifibrotic drugs in patients with early-stage IPF. Results The severity of stage I IPF (n = 179) according to the JRS criteria consisted of the following GAP staging criteria: stage I, 111 cases; stage II, 58 cases; stage III, 10 cases. The duration from the initial visit to disease progression and survival time was significantly shorter in JRS stage I patients with oxygen desaturation on the 6MWT or with increased GAP staging (unfavorable group) compared with patients without those factors. In the unfavorable group, the relative decline in percentage predicted forced vital capacity (%FVC) over 6 months was significantly lower in patients undergoing antifibrotic treatment compared with non-treated patients. Conclusion Antifibrotic drugs have a beneficial effect on the decline in %FVC in Japanese patients with early-stage IPF who have oxygen desaturation on the 6MWT or increased GAP staging.

The Combination of Schisandrol B and Wedelolactone Synergistically Reverses Hepatic Fibrosis Via Modulating Multiple Signaling Pathways in Mice

Hepatic fibrosis represents an important event in the progression of chronic liver injury to cirrhosis, and is characterized by excessive extracellular matrix proteins aggregation. Early fibrosis can be reversed by inhibiting hepatocyte injury, inflammation, or hepatic stellate cells activation, so the development of antifibrotic drugs is important to reduce the incidence of hepatic cirrhosis or even hepatic carcinoma. Here we demonstrate that Schisandrol B (SolB), one of the major active constituents of traditional hepato-protective Chinese medicine, Schisandra sphenanthera, significantly protects against hepatocyte injury, while Wedelolactone (WeD) suppresses the TGF-β1/Smads signaling pathway in hepatic stellate cells (HSCs) and inflammation, the combination of the two reverses hepatic fibrosis in mice and the inhibitory effect of the combination on hepatic fibrosis is superior to that of SolB or WeD treatment alone. Combined pharmacotherapy represents a promising strategy for the prevention and treatment of liver fibrosis.

Efficacy of early antifibrotic treatment for idiopathic pulmonary fibrosis

Background: Although antifibrotic drugs, including nintedanib and pirfenidone, slow the progression of idiopathic pulmonary fibrosis (IPF), there is little data about the timing of start of antifibrotic treatment in real-world clinical practice. The present study aimed to clarify the efficacy of nintedanib and pirfenidone in patients with early-stage IPF.Methods: We compared survival and disease progression between patients with IPF with Japanese Respiratory Society (JRS) disease severity system stage I with and without oxygen desaturation on the 6-minute walk test (6MWT) and increased the gender–age–physiology (GAP) staging. We examined the efficacy of antifibrotic drugs in patients with early-stage IPF.Results: The severity of stage I IPF (n = 179) according to the JRS criteria consisted of the following GAP staging criteria: stage I, 111 cases; stage II, 58 cases; stage III, 10 cases. The duration from the initial visit to disease progression and survival time was significantly shorter in JRS stage I patients with oxygen desaturation on the 6MWT or with increased GAP staging (unfavorable group) compared with patients without those factors. In the unfavorable group, the relative decline in percentage predicted forced vital capacity (%FVC) over 6 months was significantly lower in patients undergoing antifibrotic treatment compared with non-treated patients. Conclusion: Antifibrotic drugs have a beneficial effect on the decline in %FVC in Japanese patients with early-stage IPF who have oxygen desaturation on the 6MWT or increased GAP staging.

Progression in the Management of Non-Idiopathic Pulmonary Fibrosis Interstitial Lung Diseases, Where Are We Now and Where We Would Like to Be

A significant proportion of patients with interstitial lung disease (ILD) may develop a progressive fibrosing phenotype characterized by worsening of symptoms and pulmonary function, progressive fibrosis on chest computed tomography and increased mortality. The clinical course in these patients mimics the relentless progressiveness of idiopathic pulmonary fibrosis (IPF). Common pathophysiological mechanisms such as a shared genetic susceptibility and a common downstream pathway—self-sustaining fibroproliferation—support the concept of a progressive fibrosing phenotype, which is applicable to a broad range of non-IPF ILDs. While antifibrotic drugs became the standard of care in IPF, immunosuppressive agents are still the mainstay of treatment in non-IPF fibrosing ILD (F-ILD). However, recently, randomized placebo-controlled trials have demonstrated the efficacy and safety of antifibrotic treatment in systemic sclerosis-associated F-ILD and a broad range of F-ILDs with a progressive phenotype. This review summarizes the current pharmacological management and highlights the unmet needs in patients with non-IPF ILD.

Idiopathic interstitial pneumonias

The article presents the evolution of views on one of the current problems of present pulmonology idiopathic interstitial pneumonias. On the basis of many years of experience in diagnosis and treatment of patients of IIPs in the clinic of pulmonology of Interstitial and Orphan Lung Diseases Research Institute of Pavlov First Saint Petersburg State Medical University, the authors formulated a new understanding of this pathology and proposed to unite all IIPs under the term idiopathic fibrosing pulmonary disease. Using the concept of idiopathic fibrosing pulmonary disease will make it possible to substantively address the issues of early diagnosis, determine the criteria for the activity of the pathological process, and there by develop an evidence base for the adequate prescription of antifibrotic drugs and corticosteroids.