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1.
Am J Respir Crit Care Med ; 205(5): 495-506, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1816972

ABSTRACT

The term "advanced sarcoidosis" is used for forms of sarcoidosis with a significant risk of loss of organ function or death. Advanced sarcoidosis often involves the lung and is described as "advanced pulmonary sarcoidosis" (APS), which includes advanced pulmonary fibrosis, associated complications such as bronchiectasis and infections, and pulmonary hypertension. Although APS affects a small proportion of patients with sarcoidosis, it is the leading cause of poor outcomes, including death. Here we review the major patterns of APS with a focus on the current management as well as potential approaches for improved outcomes for this most serious sarcoidosis phenotype.


Subject(s)
Bronchiectasis , Pulmonary Fibrosis , Sarcoidosis, Pulmonary , Sarcoidosis , Humans , Lung , Sarcoidosis, Pulmonary/complications , Sarcoidosis, Pulmonary/drug therapy
2.
Molecules ; 27(9)2022 Apr 24.
Article in English | MEDLINE | ID: covidwho-1810048

ABSTRACT

Cepharanthine (CEP) has excellent anti-SARS-CoV-2 properties, indicating its favorable potential for COVID-19 treatment. However, its application is challenged by its poor dissolubility and oral bioavailability. The present study aimed to improve the bioavailability of CEP by optimizing its solubility and through a pulmonary delivery method, which improved its bioavailability by five times when compared to that through the oral delivery method (68.07% vs. 13.15%). An ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) method for quantification of CEP in rat plasma was developed and validated to support the bioavailability and pharmacokinetic studies. In addition, pulmonary fibrosis was recognized as a sequela of COVID-19 infection, warranting further evaluation of the therapeutic potential of CEP on a rat lung fibrosis model. The antifibrotic effect was assessed by analysis of lung index and histopathological examination, detection of transforming growth factor (TGF)-ß1, interleukin-6 (IL-6), α-smooth muscle actin (α-SMA), and hydroxyproline level in serum or lung tissues. Our data demonstrated that CEP could significantly alleviate bleomycin (BLM)-induced collagen accumulation and inflammation, thereby exerting protective effects against pulmonary fibrosis. Our results provide evidence supporting the hypothesis that pulmonary delivery CEP may be a promising therapy for pulmonary fibrosis associated with COVID-19 infection.


Subject(s)
COVID-19 , Pulmonary Fibrosis , Animals , Benzylisoquinolines , Biological Availability , Bleomycin/pharmacology , COVID-19/complications , COVID-19/drug therapy , Chromatography, Liquid , Humans , Lung , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/etiology , Rats , Tandem Mass Spectrometry , Transforming Growth Factor beta1/metabolism
3.
MMW Fortschr Med ; 164(8): 18, 2022 04.
Article in German | MEDLINE | ID: covidwho-1800282
5.
Tuberk Toraks ; 70(1): 111, 2022 03.
Article in English | MEDLINE | ID: covidwho-1776528
7.
Stem Cell Res Ther ; 13(1): 71, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1759775

ABSTRACT

Pulmonary fibrosis is a devastating disease that eventually leads to death and respiratory failure. Despite the wide range of drugs, including corticosteroids, endothelin antagonist, and pirfenidone, there is no effective treatment, and the only main goal of treatment is to alleviate the symptoms as much as possible to slow down the progression of the disease and improve the quality of life. Lung transplantation may be a treatment option for a few people if pulmonary fibrosis develops and there is no established treatment. Pulmonary fibrosis caused by the COVID19 virus is another problem that we face in most patients despite the efforts of the international medical communities. Therefore, achieving alternative treatment for patients is a great success. Today, basic research using stem cells on pulmonary fibrosis has published promising results. New stem cell-based therapies can be helpful in patients with pulmonary fibrosis. Wharton jelly-derived mesenchymal stem cells are easily isolated in large quantities and made available for clinical trials without causing ethical problems. These cells have higher flexibility and proliferation potential than other cells isolated from different sources and differentiated into various cells in laboratory environments. More clinical trials are needed to determine the safety and efficacy of these cells. This study will investigate the cellular and molecular mechanisms and possible effects of Wharton jelly-derived mesenchymal stem cells in pulmonary fibrosis.


Subject(s)
COVID-19 , Mesenchymal Stem Cells , Pulmonary Fibrosis , Wharton Jelly , Cell Differentiation , Humans , Pulmonary Fibrosis/therapy , Quality of Life
9.
Nutrients ; 14(5)2022 Mar 05.
Article in English | MEDLINE | ID: covidwho-1732145

ABSTRACT

BACKGROUND: Pulmonary fibrosis (PF) is a chronic, progressive, and, ultimately, terminal interstitial disease caused by a variety of factors, ranging from genetics, bacterial, and viral infections, to drugs and other influences. Varying degrees of PF and its rapid progress have been widely reported in post-COVID-19 patients and there is consequently an urgent need to develop an appropriate, cost-effective approach for the prevention and management of PF. AIM: The potential "therapeutic" effect of the tocotrienol-rich fraction (TRF) and carotene against bleomycin (BLM)-induced lung fibrosis was investigated in rats via the modulation of TGF-ß/Smad, PI3K/Akt/mTOR, and NF-κB signaling pathways. DESIGN/METHODS: Lung fibrosis was induced in Sprague-Dawley rats by a single intratracheal BLM (5 mg/kg) injection. These rats were subsequently treated with TRF (50, 100, and 200 mg/kg body wt/day), carotene (10 mg/kg body wt/day), or a combination of TRF (200 mg/kg body wt/day) and carotene (10 mg/kg body wt/day) for 28 days by gavage administration. A group of normal rats was provided with saline as a substitute for BLM as the control. Lung function and biochemical, histopathological, and molecular alterations were studied in the lung tissues. RESULTS: Both the TRF and carotene treatments were found to significantly restore the BLM-induced alterations in anti-inflammatory and antioxidant functions. The treatments appeared to show pneumoprotective effects through the upregulation of antioxidant status, downregulation of MMP-7 and inflammatory cytokine expressions, and reduction in collagen accumulation (hydroxyproline). We demonstrated that TRF and carotene ameliorate BLM-induced lung injuries through the inhibition of apoptosis, the induction of TGF-ß1/Smad, PI3K/Akt/mTOR, and NF-κB signaling pathways. Furthermore, the increased expression levels were shown to be significantly and dose-dependently downregulated by TRF (50, 100, and 200 mg/kg body wt/day) treatment in high probability. The histopathological findings further confirmed that the TRF and carotene treatments had significantly attenuated the BLM-induced lung injury in rats. CONCLUSION: The results of this study clearly indicate the ability of TRF and carotene to restore the antioxidant system and to inhibit proinflammatory cytokines. These findings, thus, revealed the potential of TRF and carotene as preventive candidates for the treatment of PF in the future.


Subject(s)
COVID-19 , Pulmonary Fibrosis , Tocotrienols , Animals , Bleomycin/toxicity , Carotenoids/adverse effects , Humans , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/prevention & control , Rats , Rats, Sprague-Dawley , SARS-CoV-2 , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Tocotrienols/adverse effects , Transforming Growth Factor beta/metabolism
10.
J Zhejiang Univ Sci B ; 23(2): 102-122, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1706587

ABSTRACT

Molecular hydrogen exerts biological effects on nearly all organs. It has anti-oxidative, anti-inflammatory, and anti-aging effects and contributes to the regulation of autophagy and cell death. As the primary organ for gas exchange, the lungs are constantly exposed to various harmful environmental irritants. Short- or long-term exposure to these harmful substances often results in lung injury, causing respiratory and lung diseases. Acute and chronic respiratory diseases have high rates of morbidity and mortality and have become a major public health concern worldwide. For example, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. An increasing number of studies have revealed that hydrogen may protect the lungs from diverse diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, and pulmonary fibrosis. In this review, we highlight the multiple functions of hydrogen and the mechanisms underlying its protective effects in various lung diseases, with a focus on its roles in disease pathogenesis and clinical significance.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Hydrogen/therapeutic use , Lung Diseases/therapy , Acute Lung Injury , Aging , Animals , Anti-Inflammatory Agents , Antioxidants/chemistry , Asthma/therapy , Autophagy , COVID-19/drug therapy , Humans , Hypertension, Pulmonary/therapy , Inflammation , Lung Neoplasms/therapy , Mice , Oxidative Stress , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Fibrosis/therapy , Pyroptosis , Reactive Oxygen Species
11.
PLoS One ; 16(10): e0259153, 2021.
Article in English | MEDLINE | ID: covidwho-1699423

ABSTRACT

PURPOSE: To determine the effects of statins and steroids on the risk of coronary artery disease (CAD) and stroke in patients with interstitial lung disease and pulmonary fibrosis (ILD-PF). METHODS: We retrospectively enrolled patients with ILD-PF who were using statins (statin cohort, N = 11,567) and not using statins (nonstatin cohort, N = 26,159). Cox proportional regression was performed to analyze the cumulative incidence of CAD and stroke. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of CAD and stroke were determined after sex, age, and comorbidities, as well as the use of inhaler corticosteroids (ICSs), oral steroids (OSs), and statins, were controlled for. RESULTS: Compared with those of patients without statin use, the aHRs (95% CIs) of patients with statin use for CAD and ischemic stroke were 0.72 (0.65-0.79) and 0.52 (0.38-0.72), respectively. For patients taking single-use statins but not ICSs/OSs, the aHRs (95% CIs) for CAD and ischemic stroke were 0.72 (0.65-0.79)/0.69 (0.61-0.79) and 0.54 (0.39-0.74)/0.50 (0.32-0.79), respectively. For patients using ICSs/OSs, the aHRs (95% CIs) for CAD and ischemic stroke were 0.71 (0.42-1.18)/0.74 (0.64-0.85) and 0.23 (0.03-1.59)/0.54 (0.35-0.85), respectively. CONCLUSIONS: The findings demonstrate that statin use, either alone or in combination with OS use, plays an auxiliary role in the management of CAD and ischemic stroke in patients with ILD-PF.


Subject(s)
Coronary Artery Disease/epidemiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lung Diseases, Interstitial/complications , Pulmonary Fibrosis/complications , Steroids/therapeutic use , Stroke/epidemiology , Coronary Artery Disease/complications , Coronary Artery Disease/prevention & control , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Incidence , Male , Middle Aged , Steroids/administration & dosage , Stroke/complications , Stroke/prevention & control
12.
Am J Case Rep ; 23: e934830, 2022 Feb 13.
Article in English | MEDLINE | ID: covidwho-1687480

ABSTRACT

BACKGROUND Physicians worldwide have been reporting many cases of COVID-19-induced pulmonary fibrosis. We report the case of a 51-year-old Filipino asthmatic woman who developed post-COVID-19 pulmonary fibrosis subsequently treated with Nintedanib. CASE REPORT The patient presented with a 4-day history of flu-like symptoms in September 2020 and was eventually diagnosed with severe COVID-19 pneumonia. Despite receiving Dexamethasone, Tocilizumab, Remdesivir, and multiple antibiotics, there was increasing oxygen requirement, necessitating ICU admission and high-flow nasal cannula (HFNC). An additional course of hydrocortisone was given due to asthma exacerbation, gradually liberating her from the HFNC. A chest CT scan showed extensive parenchymal changes, for which she received methylprednisolone and physical rehabilitation with persistence of respiratory symptoms. After 40 days of hospitalization, she was sent home on oxygen support and Nintedanib. The patient initially had severe dyspnea (Borg Scale 7) with 6-minute walk distance (6MWD) of 295 meters. Pulmonary function showed moderately severe restrictive lung defect at 52% predicted total lung capacity (TLC) and severely reduced DLCO (28% predicted). Chest CT scoring indicated severe lung involvement. One month after Nintedanib treatment, her Borg Scale improved to 4. Her 6MWD, TLC, and DLCO increased to 434 meters, 64% predicted, and 36% predicted, respectively. A chest CT scan showed regressing fibrosis. After 6 months of treatment, her pulmonary function normalized. DLCO remained moderately reduced (59% predicted) but her 6MWD (457 meters) and CT scan results continued to improve. CONCLUSIONS Nintedanib, along with other interventions, may have potentially improved pulmonary function and CT scan findings in a COVID-19 survivor with pulmonary fibrosis 6 months after treatment.


Subject(s)
COVID-19 , Pulmonary Fibrosis , Female , Humans , Lung , Middle Aged , Pulmonary Fibrosis/diagnostic imaging , Pulmonary Fibrosis/etiology , SARS-CoV-2 , Tomography, X-Ray Computed
13.
Aging (Albany NY) ; 14(3): 1110-1127, 2022 02 04.
Article in English | MEDLINE | ID: covidwho-1675399

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has induced a worldwide pandemic since early 2020. COVID-19 causes pulmonary inflammation, secondary pulmonary fibrosis (PF); however, there are still no effective treatments for PF. The present study aimed to explore the inhibitory effect of dihydroartemisinin (DHA) on pulmonary inflammation and PF, and its molecular mechanism. Morphological changes and collagen deposition were analyzed using hematoxylin-eosin staining, Masson staining, and the hydroxyproline content. DHA attenuated early alveolar inflammation and later PF in a bleomycin-induced rat PF model, and inhibited the expression of interleukin (IL)-1ß, IL-6, tumor necrosis factor α (TNFα), and chemokine (C-C Motif) Ligand 3 (CCL3) in model rat serum. Further molecular analysis revealed that both pulmonary inflammation and PF were associated with increased transforming growth factor-ß1 (TGF-ß1), Janus activated kinase 2 (JAK2), and signal transducer and activator 3(STAT3) expression in the lung tissues of model rats. DHA reduced the inflammatory response and PF in the lungs by suppressing TGF-ß1, JAK2, phosphorylated (p)-JAK2, STAT3, and p-STAT3. Thus, DHA exerts therapeutic effects against bleomycin-induced pulmonary inflammation and PF by inhibiting JAK2-STAT3 activation. DHA inhibits alveolar inflammation, and attenuates lung injury and fibrosis, possibly representing a therapeutic candidate to treat PF associated with COVID-19.


Subject(s)
Artemisinins/therapeutic use , Pneumonia/prevention & control , Pulmonary Fibrosis/prevention & control , Animals , Artemisinins/pharmacology , Janus Kinase 2/antagonists & inhibitors , Male , Rats , Rats, Wistar , STAT3 Transcription Factor/antagonists & inhibitors , Signal Transduction/drug effects
14.
Int J Mol Sci ; 23(3)2022 Jan 29.
Article in English | MEDLINE | ID: covidwho-1667195

ABSTRACT

(1) Background: In COVID-19 survivors there is an increased prevalence of pulmonary fibrosis of which the underlying molecular mechanisms are poorly understood; (2) Methods: In this multicentric study, n = 12 patients who succumbed to COVID-19 due to progressive respiratory failure were assigned to an early and late group (death within ≤7 and >7 days of hospitalization, respectively) and compared to n = 11 healthy controls; mRNA and protein expression as well as biological pathway analysis were performed to gain insights into the evolution of pulmonary fibrogenesis in COVID-19; (3) Results: Median duration of hospitalization until death was 3 (IQR25-75, 3-3.75) and 14 (12.5-14) days in the early and late group, respectively. Fifty-eight out of 770 analyzed genes showed a significantly altered expression signature in COVID-19 compared to controls in a time-dependent manner. The entire study group showed an increased expression of BST2 and IL1R1, independent of hospitalization time. In the early group there was increased activity of inflammation-related genes and pathways, while fibrosis-related genes (particularly PDGFRB) and pathways dominated in the late group; (4) Conclusions: After the first week of hospitalization, there is a shift from pro-inflammatory to fibrogenic activity in severe COVID-19. IL1R1 and PDGFRB may serve as potential therapeutic targets in future studies.


Subject(s)
COVID-19/genetics , COVID-19/metabolism , Pulmonary Fibrosis/pathology , Aged , COVID-19/mortality , Female , Hospital Mortality/trends , Hospitalization , Humans , Lung/pathology , Male , Middle Aged , Pulmonary Fibrosis/metabolism , Respiratory Insufficiency/pathology , SARS-CoV-2/pathogenicity
15.
Medicine (Baltimore) ; 101(3): e28639, 2022 Jan 21.
Article in English | MEDLINE | ID: covidwho-1642427

ABSTRACT

ABSTRACT: The development of pulmonary fibrosis is a rare complication of the novel coronavirus disease 2019 (COVID-19). Limited information is available in the literature about that, and the present study aimed to address this gap.This case-control study included 64 patients with post-COVID-19 pulmonary fibrosis who were hospitalized for COVID-19.The percentage of patients aged ≥65 years (44%) who demised was higher than those who survived (25%). Male patients (62%) had higher mortality than female patients (37%). The most frequently reported clinical symptoms were shortness of breath (98%), cough (91%), and fever (70%). Most COVID-19 patients with pulmonary fibrosis (81%) were admitted to an intensive care unit (ICU), and 63% required mechanical ventilation. Bilateral lung infiltrates (94%), "ground glass" opacity (91%), "honeycomb" lung (25%), and pulmonary consolidation (9%) were commonly identified in COVID-19 patients with pulmonary fibrosis who survived. The findings for computed tomography and dyspnea scale were significantly higher in severe cases admitted to the ICU who required mechanical ventilation. A higher computerized tomography score also correlated significantly with a longer duration of stay in hospital and a higher degree of dyspnea. Half of the COVID-19 patients with pulmonary fibrosis (50%) who survived required oxygen therapy, and those with "honeycomb" lung required long-term oxygen therapy to a far greater extent than others. Cox regression revealed that smoking and asthma were significantly associated with ICU admission and the risk of mortality.Post-COVID-19 pulmonary fibrosis is a severe complication that leads to permanent lung damage or death.


Subject(s)
COVID-19/complications , Lung/diagnostic imaging , Adrenal Cortex Hormones/therapeutic use , Anticoagulants/therapeutic use , COVID-19/epidemiology , Case-Control Studies , Cough/etiology , Dyspnea/etiology , Female , Fever/etiology , Humans , Intensive Care Units , Male , Oxygen , Prednisolone/therapeutic use , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/therapy , Retrospective Studies , SARS-CoV-2 , Saudi Arabia/epidemiology , Tomography, X-Ray Computed , Vitamins/therapeutic use
16.
Chest ; 161(1): 169-178, 2022 01.
Article in English | MEDLINE | ID: covidwho-1616416

ABSTRACT

The COVID-19 pandemic has caused acute lung injury in millions of individuals worldwide. Some patients develop COVID-related acute respiratory distress syndrome (CARDS) and cannot be liberated from mechanical ventilation. Others may develop post-COVID fibrosis, resulting in substantial disability and need for long-term supplemental oxygen. In both of these situations, treatment teams often inquire about the possibility of lung transplantation. In fact, lung transplantation has been successfully employed for both CARDS and post-COVID fibrosis in a limited number of patients worldwide. Lung transplantation after COVID infection presents a number of unique challenges that transplant programs must consider. In those with severe CARDS, the inability to conduct proper psychosocial evaluation and pretransplantation education, marked deconditioning from critical illness, and infectious concerns regarding viral reactivation are major hurdles. In those with post-COVID fibrosis, our limited knowledge about the natural history of recovery after COVID-19 infection is problematic. Increased knowledge of the likelihood and degree of recovery after COVID-19 acute lung injury is essential for appropriate decision-making with regard to transplantation. Transplant physicians must weigh the risks and benefits of lung transplantation differently in a post-COVID fibrosis patient who is likely to remain stable or gradually improve in comparison with a patient with a known progressive fibrosing interstitial lung disease (fILD). Clearly lung transplantation can be a life-saving therapeutic option for some patients with severe lung injury from COVID-19 infection. In this review, we discuss how lung transplant providers from a number of experienced centers approach lung transplantation for CARDS or post-COVID fibrosis.


Subject(s)
COVID-19/surgery , Lung Transplantation , Pneumonia, Viral/surgery , Pulmonary Fibrosis/surgery , Humans , Pandemics , Pneumonia, Viral/virology , Pulmonary Fibrosis/virology , SARS-CoV-2
17.
Medicine (Baltimore) ; 100(47): e27980, 2021 Nov 24.
Article in English | MEDLINE | ID: covidwho-1604285

ABSTRACT

RATIONALE: Pulmonary fibrosis is an infamous sequela of coronavirus disease 2019 (COVID-19) pneumonia leading to long-lasting respiratory problems and activity limitations. Pulmonary rehabilitation is beneficial to improve the symptoms of lung fibrosis. We experienced a post-COVID-19 pulmonary fibrosis patient who received a structured exercise-based pulmonary rehabilitation program. PATIENT CONCERNS: This article presents a case of successful pulmonary rehabilitation of a patient with post-COVID-19 pulmonary fibrosis. The patient could not cut off the oxygen supplement even after a successful recovery from COVID-19. DIAGNOSIS: Diagnosis of COVID-19 was based on the reverse transcription-polymerase chain reaction (RT-PCR). Pulmonary fibrosis was diagnosed by patient's complaint, clinical appearance, and computed tomography (CT) on chest. INTERVENTION: The patient underwent ten sessions of exercise-based rehabilitation program according to Consensus Document on Pulmonary Rehabilitation in Korea, 2015. OUTCOME: On the 8th day, he could cut off the oxygen supplementation and complete the one-hour exercise without oxygen. He was discharged after completing the 10-session program without any activity limitations. LESSONS: Exercise-based pulmonary rehabilitation will help the post-COVID-19 pulmonary fibrosis patients. This case suggested the importance of pulmonary rehabilitation program to the post-COVID-19 pulmonary fibrosis patient.


Subject(s)
COVID-19/complications , Lung/diagnostic imaging , Pulmonary Fibrosis/rehabilitation , COVID-19/diagnosis , COVID-19 Testing , Humans , Lung/pathology , Male , Middle Aged , Oxygen , Pulmonary Fibrosis/diagnostic imaging , Pulmonary Fibrosis/etiology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Tomography, X-Ray Computed
18.
Am J Chin Med ; 50(1): 33-51, 2022.
Article in English | MEDLINE | ID: covidwho-1608685

ABSTRACT

Qingfei Paidu decoction (QFPD) has been repeatedly recommended for the clinical treatment of novel coronavirus disease 2019 (COVID-19) in multiple provinces throughout China. A possible complication of COVID-19 lung involvement is pulmonary fibrosis, which causes chronic breathing difficulties and affects the patient's quality of life. Therefore, there is an important question regarding whether QFPD can alleviate the process of pulmonary fibrosis and its potential mechanisms. To explore this issue, this study demonstrated the anti-pulmonary fibrosis activity and mode of action of QFPD in vivo and in vitro pulmonary fibrosis models and network pharmacology. The results showed that QFPD effectively ameliorated the bleomycin-induced inflammation and collagen deposition in mice and significantly improved the epithelial-mesenchymal transition in pulmonary fibrosis in mice. In addition, QFPD inhibited bleomycin-induced M2 polarization of macrophages in pulmonary tissues. An in-depth study of the mechanism of QFPD in the treatment of pulmonary fibrosis based on network pharmacology and molecular simulation revealed that SRC was the main target of QFPD and sitosterol (a key compound in QFPD). QFPD and sitosterol regulate the EMT process and M2 polarization of macrophages by inhibiting the activation of SRC, thereby alleviating pulmonary fibrosis in mice. COVID-19 infection might produce severe fibrosis, and antifibrotic therapy with QFPD may be valuable in preventing severe neocoronavirus disease in patients with IPF, which could be a key factor explaining the role of QFPD in the treatment of COVID-19.


Subject(s)
COVID-19 , Pulmonary Fibrosis , Animals , Drugs, Chinese Herbal , Epithelial-Mesenchymal Transition , Humans , Mice , Mice, Inbred C57BL , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology , Quality of Life , SARS-CoV-2
19.
BMJ Open Respir Res ; 8(1)2021 12.
Article in English | MEDLINE | ID: covidwho-1595592

ABSTRACT

INTRODUCTION: Recent discoveries have identified shortened telomeres and related mutations in people with pulmonary fibrosis (PF). There is evidence to suggest that androgens, including danazol, may be effective in lengthening telomeres in peripheral blood cells. This study aims to assess the safety and efficacy of danazol in adults and children with PF associated with telomere shortening. METHODS AND ANALYSIS: A multi-centre, double-blind, placebo-controlled, randomised trial of danazol will be conducted in subjects aged >5 years with PF associated with age-adjusted telomere length ≤10th centile measured by flow fluorescence in situ hybridisation; or in children, a diagnosis of dyskeratosis congenita. Adult participants will receive danazol 800 mg daily in two divided doses or identical placebo capsules orally for 12 months, in addition to standard of care (including pirfenidone or nintedanib). Paediatric participants will receive danazol 2 mg/kg/day orally in two divided doses or identical placebo for 6 months. If no side effects are encountered, the dose will be escalated to 4 mg/kg/day (maximum 800 mg daily) orally in two divided doses for a further 6 months. The primary outcome is change in absolute telomere length in base pairs, measured using the telomere shortest length assay (TeSLA), at 12 months in the intention to treat population. ETHICS AND DISSEMINATION: Ethics approval has been granted in Australia by the Metro South Human Research Ethics Committee (HREC/2020/QMS/66385). The study will be conducted and reported according to Standard Protocol Items: Recommendations for Interventional Trials guidelines. Results will be published in peer-reviewed journals and presented at international and national conferences. TRIAL REGISTRATION NUMBERS: NCT04638517; Australian New Zealand Clinical Trials Registry (ACTRN12620001363976p).


Subject(s)
COVID-19 , Pulmonary Fibrosis , Australia , Child , Danazol/therapeutic use , Humans , Telomere/genetics , Treatment Outcome
20.
Am J Chin Med ; 49(8): 1965-1999, 2021.
Article in English | MEDLINE | ID: covidwho-1599109

ABSTRACT

Pulmonary fibrosis (PF) is a chronic and irreversible interstitial lung disease that even threatens the lives of some patients infected with COVID-19. PF is a multicellular pathological process, including the initial injuries of epithelial cells, recruitment of inflammatory cells, epithelial-mesenchymal transition, activation and differentiation of fibroblasts, etc. TGF-[Formula: see text]1 acts as a key effect factor that participates in these cellular processes of PF. Recently, much attention was paid to inhibiting TGF-[Formula: see text]1 mediated cell processes in the treatment of PF with Chinese herbal medicines (CHM), an important part of traditional Chinese medicine. Here, this review first summarized the effects of TGF-[Formula: see text]1 in different cellular processes of PF. Then, this review summarized the recent research on CHM (compounds, multi-components, single medicines and prescriptions) to directly and/or indirectly inhibit TGF-[Formula: see text]1 signaling (TLRs, PPARs, micrRNA, etc.) in PF. Most of the research focused on CHM natural compounds, including but not limited to alkaloids, flavonoids, phenols and terpenes. After review, the research perspectives of CHM on TGF-[Formula: see text]1 inhibition in PF were further discussed. This review hopes that revealing the inhibiting effects of CHM on TGF-[Formula: see text]1-mediated cellular processes of PF can promote CHM to be better understood and utilized, thus transforming the therapeutic activities of CHM into practice.


Subject(s)
Cell Physiological Phenomena/drug effects , Drugs, Chinese Herbal/therapeutic use , Pulmonary Fibrosis/drug therapy , Signal Transduction/drug effects , Transforming Growth Factor beta1/antagonists & inhibitors , COVID-19/complications , COVID-19/metabolism , COVID-19/virology , Humans , Medicine, Chinese Traditional/methods , Phytotherapy/methods , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/metabolism , SARS-CoV-2/physiology , Transforming Growth Factor beta1/metabolism
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