Eur Respir J. 2023 May 18;61(5):2300653. doi: 10.1183/13993003.00653-2023. Print 2023 May.

NO ABSTRACT

PMID:37208038 | DOI:10.1183/13993003.00653-2023

J Ethnopharmacol. 2023 May 17:116633. doi: 10.1016/j.jep.2023.116633. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Fu-Zheng-Tong-Luo (FZTL) formula is a Chinese herbal prescription which is used to treat idiopathic pulmonary fibrosis (IPF). We previously reported that the FZTL formula could improve IPF injury in rats; however, the mechanism remains unelucidated.

AIM OF THE STUDY: To elucidate the effects and mechanisms of the FZTL formula on IPF.

MATERIALS AND METHODS: The bleomycin-induced pulmonary fibrosis rat model and transforming growth factor-β-induced lung fibroblast model were used. Histological changes and fibrosis formation were detected in the rat model after treatment with the FZTL formula. Furthermore, the effects of the FZTL formula on autophagy and lung fibroblast activation were determined. Moreover, the mechanism of FZTL was explored using transcriptomics analysis.

RESULTS: We observed that FZTL alleviated IPF injury in rats and inhibited inflammatory responses and fibrosis formation in rats. Moreover, it promoted autophagy and inhibited lung fibroblast activation in vitro. Transcriptomics analysis revealed that FZTL regulates the Janus kinase 2 (JAK)/signal transducer and activator of the transcription 3 (STAT) signaling pathway. The JAK2/STAT3 signaling activator interleukin 6 inhibited the anti-fibroblast activation effect of the FZTL formula. Combined treatment with the JAK2 inhibitor (AZD1480) and autophagy inhibitor (3-methyladenine) did not enhance the antifibrotic effect of FZTL.

CONCLUSIONS: The FZTL formula can inhibit IPF injury and lung fibroblast activation. Its effects are mediated via the JAK2/STAT3 signaling pathway. The FZTL formula may be a potential complementary therapy for pulmonary fibrosis.

PMID:37207878 | DOI:10.1016/j.jep.2023.116633

Minerva Med. 2023 May 19. doi: 10.23736/S0026-4806.23.08585-3. Online ahead of print.

ABSTRACT

BACKGROUND: During the last decade, a number of clinical scores, such as Gender-Age-Physiology (GAP) Index, TORVAN Score and Charlson Comorbidity Index (CCI), have been separately used to measure comorbidity burden in idiopathic pulmonary fibrosis (IPF). However, no previous study compared the prognostic value of these scores to assess mortality risk stratification in IPF patients with mild-to-moderate disease.

METHODS: All consecutive patients with mild-to-moderate IPF who underwent high-resolution computed tomography, spirometry, transthoracic echocardiography and carotid ultrasonography at our Institution, between January 2016 and December 2018, were retrospectively analyzed. GAP Index, TORVAN Score and CCI were calculated in all patients. Primary endpoint was all-cause mortality, whereas secondary endpoint was the composite of all-cause mortality and rehospitalizations for all-causes, over medium-term follow-up.

RESULTS: Seventy IPF patients (70.2±7.4 yrs, 74.3% males) were examined. At baseline, GAP Index, TORVAN Score and CCI were 3.4±1.1, 14.7±4.1 and 5.3±2.4, respectively. A strong correlation between coronary artery calcification (CAC) and common carotid artery (CCA) intima-media thickness (IMT) (r=0.88), CCI and CAC (r=0.80), CCI and CCA-IMT (r=0.81), was demonstrated in the study group. Follow-up period was 3.5±1.2 years. During follow-up, 19 patients died and 32 rehospitalizations were detected. CCI (HR 2.39, 95% CI: 1.31-4.35) and heart rate (HR 1.10, 95% CI: 1.04-1.17) were independently associated with primary endpoint. CCI (HR 1.54, 95% CI: 1.15-2.06) predicted secondary endpoint, also. A CCI ≥6 was the optimal cut-off for predicting both outcomes.

CONCLUSIONS: Due to the increased atherosclerotic and comorbidity burden, IPF patients with CCI ≥6 at an early-stage disease have poor outcome over medium-term follow-up.

PMID:37204783 | DOI:10.23736/S0026-4806.23.08585-3

Eur Respir J. 2023 May 18:2300291. doi: 10.1183/13993003.00291-2023. Online ahead of print.

ABSTRACT

BACKGROUND: We aimed to study whether statin use is associated with lowering the development of interstitial lung disease (ILD) or idiopathic pulmonary fibrosis (IPF).

METHODS: The study population was the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS). ILD and IPF cases were identified using the diagnosis codes (J84.1 for ILD and J84.1A for special code for IPF) based on the International Classification of Diseases, 10th revision codes. The study participants were followed up from January 1, 2004 to December 31, 2015. Statins use was defined by the cumulative defined daily dose per 2-year interval and categorized into never-use, less than 182.5, 182.5 to 365.0, 365.0 to 547.5, and 547.5 or more. A Cox model was used to fit a model with a time-dependent variable of statin use.

RESULTS: Incidence rates for ILD with and without statin use were 20.0 and 44.8/100 000 person-year, respectively and those for IPF were 15.6 and 19.3/100 000 person-year, respectively. The use of statins was independently associated with a lower incidence of ILD and IPF in a dose-response fashion (p's for trend<0.001). ILD showed adjusted hazard ratios (aHRs) 1.02 (95% confidence interval (CI) 0.87-1.20), 0.60 (0.47-0.77), 0.27 (0.16-0.45) and 0.24 (0.13-0.42) according to the increasing category of statin use compared to the never-use. IPF showed aHRs 1.29 (1.07-1.57), 0.74 (0.57-0.96), 0.40 (0.25-0.64) and 0.21 (0.11-0.41), respectively.

INTERPRETATION: A population-based cohort analysis found that statin use is independently associated with a decreased risk of ILD and IPF in a dose-response manner.

PMID:37202155 | DOI:10.1183/13993003.00291-2023

Acta Radiol. 2023 May 17:2841851231175252. doi: 10.1177/02841851231175252. Online ahead of print.

ABSTRACT

BACKGROUND: Quantitative analyses of computed tomography (CT) images using computer-aided detection (CAD) are correlated with visual assessments and pulmonary function test findings and might be useful for predicting the prognosis of patients with idiopathic pulmonary fibrosis (IPF).

PURPOSE: To evaluate the association between the quantitative analysis of long-term follow-up CT of IPF and the progression and prognosis.

MATERIAL AND METHODS: A total of 48 patients with IPF who received over one year of follow-up CT were included in this study. The results of quantitative analyses (emphysema, ground-glass attenuation [GGA], consolidation, reticulation, and honeycombing) using a CAD software program of initial and follow-up CT findings were evaluated, and the association with the progression of the total lesion of IPF and prognosis using Spearman's rank correlation and Cox regression analyses was considered.

RESULTS: Results of quantitative analyses of consolidation, reticulation, honeycombing, and the total lesion on initial CT were correlated with progressive changes in the total lesion of IPF per year (r = 0.4375, 0.4128, 0.4649, and 0.4095, respectively). The results of quantitative analyses of honeycombing (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.03-1.89, P = 0.0314) and GGA (HR = 0.85, 95% CI = 0.72-0.99, P = 0.0384) at initial CT were prognostic factors according to a multivariate Cox regression analysis.

CONCLUSION: The quantitative analysis of honeycombing using a CAD software program of CT findings may be useful for predicting the progression and prognosis of patients with IPF.

PMID:37198911 | DOI:10.1177/02841851231175252

Transl Lung Cancer Res. 2023 Apr 28;12(4):719-726. doi: 10.21037/tlcr-22-699. Epub 2023 Apr 3.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a risk factor for mortality in patients with lung cancer. Nintedanib has been known to slow down the decline of lung function and reduce IPF exacerbation. We aimed to explore the feasibility of adding nintedanib to chemotherapy for non-small cell lung cancer (NSCLC) patients with IPF.

METHODS: Chemotherapy-naïve stage III or IV NSCLC patients with IPF were prospectively enrolled and received carboplatin plus paclitaxel with nintedanib. Primary endpoint was incidence of treatment-related acute exacerbation of IPF within 8 weeks after the last administration of chemotherapy. We initially planned to enroll 30 patients and consider it feasible when the incident rate is less than 10%. Secondary endpoint was progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and disease control rate (DCR).

RESULTS: After 27 patients were enrolled, trial was early terminated because 4 patients (14.8%) experienced exacerbation. Median PFS and OS were 5.4 months [95% confidence interval (CI): 4.6-9.3] and 15.8 months (95% CI: 12.2-30.1), respectively. ORR and DCR were 40.7% (95% CI: 24.5-59.2%) and 88.9% (95% CI: 71.9-96.1%), respectively. One patient discontinued trial treatment due to neuropathy.

CONCLUSIONS: Although the primary endpoint was not met, there might be a survival benefit. The addition of nintedanib to chemotherapy might be useful in selected population.

PMID:37197621 | PMC:PMC10183406 | DOI:10.21037/tlcr-22-699

Respir Res. 2023 May 16;24(1):132. doi: 10.1186/s12931-023-02421-6.

ABSTRACT

BACKGROUND: Myo-inositol (or inositol) and its derivatives not only function as important metabolites for multiple cellular processes but also act as co-factors and second messengers in signaling pathways. Although inositol supplementation has been widely studied in various clinical trials, little is known about its effect on idiopathic pulmonary fibrosis (IPF). Recent studies have demonstrated that IPF lung fibroblasts display arginine dependency due to loss of argininosuccinate synthase 1 (ASS1). However, the metabolic mechanisms underlying ASS1 deficiency and its functional consequence in fibrogenic processes are yet to be elucidated.

METHODS: Metabolites extracted from primary lung fibroblasts with different ASS1 status were subjected to untargeted metabolomics analysis. An association of ASS1 deficiency with inositol and its signaling in lung fibroblasts was assessed using molecular biology assays. The therapeutic potential of inositol supplementation in fibroblast phenotypes and lung fibrosis was evaluated in cell-based studies and a bleomycin animal model, respectively.

RESULTS: Our metabolomics studies showed that ASS1-deficient lung fibroblasts derived from IPF patients had significantly altered inositol phosphate metabolism. We observed that decreased inositol-4-monophosphate abundance and increased inositol abundance were associated with ASS1 expression in fibroblasts. Furthermore, genetic knockdown of ASS1 expression in primary normal lung fibroblasts led to the activation of inositol-mediated signalosomes, including EGFR and PKC signaling. Treatment with inositol significantly downregulated ASS1 deficiency-mediated signaling pathways and reduced cell invasiveness in IPF lung fibroblasts. Notably, inositol supplementation also mitigated bleomycin-induced fibrotic lesions and collagen deposition in mice.

CONCLUSION: These findings taken together demonstrate a novel function of inositol in fibrometabolism and pulmonary fibrosis. Our study provides new evidence for the antifibrotic activity of this metabolite and suggests that inositol supplementation may be a promising therapeutic strategy for IPF.

PMID:37194070 | DOI:10.1186/s12931-023-02421-6

Am J Respir Cell Mol Biol. 2023 May 16. doi: 10.1165/rcmb.2022-0304OC. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible interstitial pneumonia caused by the excessive production and deposition of extracellular matrix components, including type I collagen. Activated fibroblasts, called α-smooth muscle actin (α-SMA)-expressing myofibroblasts, are the major source of type I collagen in pulmonary fibrosis (PF), but the mechanisms underlying disease progression have not been fully elucidated. Here, we obtained lung fibroblasts from IPF patients from both non-fibrotic and fibrotic areas as determined by a lung computed tomography scan, and compared gene expression between these areas by DNA microarray. We found that angiopoietin-like 4 (ANGPTL4) was highly expressed only in fibroblasts from the fibrotic area. ANGPTL4 was selectively expressed in the fibroblastic area of IPF lungs, where the myofibroblast marker α-SMA was also expressed. ANGPTL4 also regulates the gene expression of fibrosis-related markers, cell migration and proliferation. In addition, ANGPTL4 expression in a murine model of PF induced by treatment with bleomycin was significantly induced in the lungs from the acute to the chronic phase. Single-cell transcriptome analysis during the course of bleomycin-induced PF revealed that Angptl4 was predominantly expressed in the activated fibroblasts and myofibroblasts. Moreover, the administration of recombinant ANGPTL4 to the bleomycin-induced fibrosis model significantly increased collagen deposition and exacerbated the PF. In contrast, the pathogenesis of PF in Angptl4-deficient mice was improved. These results indicate that ANGPTL4 is critical for the progression of PF, and might be an early diagnostic marker and therapeutic target for IPF.

PMID:37192434 | DOI:10.1165/rcmb.2022-0304OC

Biomedicines. 2023 Mar 28;11(4):1047. doi: 10.3390/biomedicines11041047.

ABSTRACT

Genetic information is not transmitted solely by DNA but by the epigenetics process. Epigenetics describes molecular missing link pathways that could bridge the gap between the genetic background and environmental risk factors that contribute to the pathogenesis of pulmonary fibrosis. Specific epigenetic patterns, especially DNA methylation, histone modifications, long non-coding, and microRNA (miRNAs), affect the endophenotypes underlying the development of idiopathic pulmonary fibrosis (IPF). Among all the epigenetic marks, DNA methylation modifications have been the most widely studied in IPF. This review summarizes the current knowledge concerning DNA methylation changes in pulmonary fibrosis and demonstrates a promising novel epigenetics-based precision medicine.

PMID:37189665 | DOI:10.3390/biomedicines11041047

Chest. 2023 May 13:S0012-3692(23)00669-4. doi: 10.1016/j.chest.2023.05.013. Online ahead of print.

ABSTRACT

BACKGROUND: Obstructive sleep apnea (OSA) and nocturnal hypoxemia (NH) are common in patients with fibrotic interstitial lung disease (F-ILD), but their relationship with disease outcomes remains unclear.

RESEARCH QUESTIONS: What is the relationship between NH and OSA and clinical outcomes in patients with F-ILD?

STUDY DESIGN AND METHODS: Prospective observational cohort study of patients with F-ILD and without daytime hypoxemia. Subjects underwent home sleep study at baseline and were followed up for at least one year or until death. NH was defined as ≥ 10% of sleep with SpO2 <90%. OSA was defined as an apnea-hypopnea index of ≥ 15/hour.

RESULTS: Among 102 (male 74.5%; age 73.0 ± 8.7 years; FVC 2.74 ± 0.78L; 91.1% idiopathic pulmonary fibrosis) participants, 20 (19.6%) demonstrated prolonged nocturnal hypoxemia (NH), and 32 (31.4%) had obstructive sleep apnea (OSA). There were no significant differences between those with and without NH or OSA at baseline. Despite this, nocturnal hypoxemia was associated with a more rapid decline in both quality of life as measured by the King's Brief Interstitial Lung Disease questionnaire (change -11.3 ± 5.3 points in the NH group vs -6.7 ± 6.5 in those without NH, p=0.005) and higher all-cause mortality at one year (HR 8.21; 95% CI 2.40-28.1, p<0.001). No statistically significant difference was seen between the groups in annualised change in measures of pulmonary function testing.

INTERPRETATION: Prolonged NH but not OSA is associated with worsening disease-related quality of life and increased mortality in patients with F-ILD.

PMID:37187434 | DOI:10.1016/j.chest.2023.05.013

J Heart Lung Transplant. 2023 May 13:S1053-2498(23)01854-5. doi: 10.1016/j.healun.2023.05.007. Online ahead of print.

ABSTRACT

BACKGROUND: Coronary artery disease (CAD) is common among lung transplant (LTx) candidates and has historically been viewed as a contraindication to the procedure. Survival outcomes of lung transplant recipients with concomitant coronary artery disease who had prior or perioperative revascularization remain a topic of conversation.

METHODS: A retrospective analysis of all single and double lung transplant patients from Feb-2012 to Aug-2021 at a single center was performed (n = 880). Patients were split into 4 groups: (1) those who received a preoperative percutaneous coronary intervention, (2) those who received pre-operative coronary artery bypass grafting (CABG), (3) those who received CABG during transplantation, and (4) those who had lung transplantation without revascularization. Groups were compared for demographics, surgical procedure, and survival outcomes using STATA Inc. P-value <0.05 was considered significant.

RESULTS: Most patients receiving LTx were males = and white. Pump type (p 0.810), total ischemic time (p 0.994), warm ischemic time (p 0.479), length of stay (p 0.751), and lung allocation score (p 0.332) were not significantly different between the four groups. The no revascularization group was younger than the other groups (p<0.01). The diagnosis of Idiopathic Pulmonary Fibrosis was predominant in all groups except the no revascularization group. The pre-CABG group had a higher portion of single LTx procedures (p 0.014). Kaplan-Meier analysis showed no significantly different survival rates after post-LTx between the groups (p 0.471). Cox Regression analysis showed diagnosis significantly impacted survival rates (p 0.009).

CONCLUSIONS: Preoperative or intraoperative revascularization did not affect survival outcomes in lung transplant patients. Selected patients with coronary artery disease may benefit when intervened during lung transplant procedures.

PMID:37187320 | DOI:10.1016/j.healun.2023.05.007

Curr Issues Mol Biol. 2023 Apr 5;45(4):3122-3145. doi: 10.3390/cimb45040204.

ABSTRACT

Transposable elements are important sources of miRNA, long non-coding RNAs genes, and their targets in the composition of protein-coding genes in plants and animals. Therefore, the detection of expression levels of specific non-coding RNAs in various tissues and cells in normal and pathological conditions may indicate a programmed pattern of transposable elements' activation. This reflects the species-specific composition and distribution of transposable elements in genomes, which underlie gene regulation in every cell division, including during aging. TEs' expression is also regulated by epigenetic factors (DNA methylation, histone modifications), SIRT6, cytidine deaminases APOBEC3, APOBEC1, and other catalytic proteins, such as ERCC, TREX1, RB1, HELLS, and MEGP2. In evolution, protein-coding genes and their regulatory elements are derived from transposons. As part of non-coding regions and introns of genes, they are sensors for transcriptional and post-transcriptional control of expression, using miRNAs and long non-coding RNAs, that arose from transposable elements in evolution. Methods (Orbld, ncRNAclassifier) and databases have been created for determining the occurrence of miRNAs from transposable elements in plants (PlanTE-MIR DB, PlaNC-TE), which can be used to design epigenetic gene networks in ontogenesis. Based on the data accumulated in the scientific literature, the presence of 467 transposon-derived miRNA genes in the human genome has been reliably established. It was proposed to create an updated and controlled online bioinformatics database of miRNAs derived from transposable elements in healthy individuals, as well as expression changes of these miRNAs during aging and various diseases, such as cancer and difficult-to-treat diseases. The use of the information obtained can open new horizons in the management of tissue and organ differentiation to aging slow down. In addition, the created database could become the basis for clarifying the mechanisms of pathogenesis of various diseases (imbalance in the activity of transposable elements, reflected in changes in the expression of miRNAs) and designing their targeted therapy using specific miRNAs as targets. This article provides examples of the detection of transposable elements-derived miRNAs involved in the development of specific malignant neoplasms, aging, and idiopathic pulmonary fibrosis.

PMID:37185728 | DOI:10.3390/cimb45040204

Am J Respir Crit Care Med. 2023 May 15;207(10):1411. doi: 10.1164/rccm.v207erratum4.

NO ABSTRACT

PMID:37184419 | DOI:10.1164/rccm.v207erratum4

Expert Opin Pharmacother. 2023 May 15. doi: 10.1080/14656566.2023.2213436. Online ahead of print.

ABSTRACT

INTRODUCTION: Idiopathic Pulmonary Fibrosis (IPF) is a progressive and devastating lung disease, characterized by progressive lung scarring.

AREAS COVERED: Prior to antifibrotic therapy (pirfenidone and nintedanib), there was no validated pharmaceutical therapy for IPF. Both antifibrotics can slow disease progression, however, IPF remains a detrimental disease with poor prognosis and treated survival rates of less than 7 years from diagnosis. Despite their effect the disease remains non-reversible and progressing whilst their side effect profile is often challenging. Treatment of comorbidities is also crucial. In this review, we discuss the current pharmacological management as well as management of comorbidities and symptoms. We also reviewed clinicaltrials.gov and summarised all the mid to late stage clinical trials (phase II and III) registered in IPF over the last 7 years and discuss the most promising drugs in clinical development.

EXPERT OPINION: Future for IPF management will need to focus on current unresolved issues. First a primary pathogenetic pathway has not been clearly identified. Future management may involve a combination of brushstroke approach with antifibrotics with targeted treatments for specific pathways in patient subsets following an 'oncological' approach. Another unmet need is management of exacerbations, which are deathly in most cases as well as either treating or preventing lung cancer.

PMID:37183672 | DOI:10.1080/14656566.2023.2213436

Phys Ther Res. 2023;26(1):32-37. doi: 10.1298/ptr.E10218. Epub 2023 Feb 14.

ABSTRACT

OBJECTIVE: Interstitial lung disease (ILD) is classified into several disease groups. Among them, idiopathic pulmonary fibrosis (IPF) has higher incidence and poor prognosis; therefore, it is important to characterize specific IPF symptoms. Exercise desaturation is a strong factor related to mortality in patients with ILD. Thus, the purpose of this study was to compare the degree of oxygen desaturation between IPF and other ILD (non-IPF ILD) patients during exercise, using the 6-minute walk test (6MWT).

METHODS: This retrospective study included 126 stable patients with ILD who underwent 6MWT in our outpatient department. The 6MWT was used to assess desaturation during exercise, 6-minute walk distance (6MWD), and dyspnea at the end of exercise. In addition, patient characteristics and pulmonary function test results were recorded.

RESULTS: Study subjects were divided into 51 IPF patients and 75 non-IPF ILD patients. The IPF group had significantly lower nadir oxygen saturation determined by pulse oximetry (SpO2) during 6MWT than the non-IPF ILD group (IPF, 86.5 ± 4.6%; non-IPF ILD, 88.7 ± 5.3%; p = 0.02). The significant association between the nadir SpO2 and IPF or non-IPF ILD grouping remained even after adjusting for gender, age, body mass index, lung function, 6MWD, and dyspnea (β = -1.62; p <0.05).

CONCLUSION: Even after adjusting for confounding factors, IPF patients had lower nadir SpO2 during 6MWT. Early assessment of exercise desaturation using the 6MWT may be more important in patients with IPF compared with patients with other ILDs.

PMID:37181481 | PMC:PMC10169312 | DOI:10.1298/ptr.E10218

Front Med (Lausanne). 2023 Apr 27;10:1152211. doi: 10.3389/fmed.2023.1152211. eCollection 2023.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic, rare progressive lung disease, characterized by lung scarring and the irreversible loss of lung function. Two anti-fibrotic drugs, nintedanib and pirfenidone, have been demonstrated to slow down disease progression, although IPF mortality remains a challenge and the patients die after a few years from diagnosis. Rare pathogenic variants in genes that are involved in the surfactant metabolism and telomere maintenance, among others, have a high penetrance and tend to co-segregate with the disease in families. Common recurrent variants in the population with modest effect sizes have been also associated with the disease risk and progression. Genome-wide association studies (GWAS) support at least 23 genetic risk loci, linking the disease pathogenesis with unexpected molecular pathways including cellular adhesion and signaling, wound healing, barrier function, airway clearance, and innate immunity and host defense, besides the surfactant metabolism and telomere biology. As the cost of high-throughput genomic technologies continuously decreases and new technologies and approaches arise, their widespread use by clinicians and researchers is efficiently contributing to a better understanding of the pathogenesis of progressive pulmonary fibrosis. Here we provide an overview of the genetic factors known to be involved in IPF pathogenesis and discuss how they will continue to further advance in this field. We also discuss how genomic technologies could help to further improve IPF diagnosis and prognosis as well as for assessing genetic risk in unaffected relatives. The development and validation of evidence-based guidelines for genetic-based screening of IPF will allow redefining and classifying this disease relying on molecular characteristics and contribute to the implementation of precision medicine approaches.

PMID:37181377 | PMC:PMC10172674 | DOI:10.3389/fmed.2023.1152211

Int J Mol Sci. 2023 May 5;24(9):8333. doi: 10.3390/ijms24098333.

ABSTRACT

Silicosis, characterized by irreversible pulmonary fibrosis, remains a major global public health problem. Nowadays, cumulative studies are focusing on elucidating the pathogenesis of silicosis in order to identify preventive or therapeutic antifibrotic agents. However, the existing research on the mechanism of silica-dust-induced pulmonary fibrosis is only the tip of the iceberg and lags far behind clinical needs. Idiopathic pulmonary fibrosis (IPF), as a pulmonary fibrosis disease, also has the same problem. In this study, we examined the relationship between silicosis and IPF from the perspective of their pathogenesis and fibrotic characteristics, further discussing current drug research and limitations of clinical application in silicosis. Overall, this review provided novel insights for clinical treatment of silicosis with the hope of bridging the gap between research and practice in silicosis.

PMID:37176040 | DOI:10.3390/ijms24098333

Int J Mol Sci. 2023 Apr 25;24(9):7849. doi: 10.3390/ijms24097849.

ABSTRACT

Pirfenidone and nintedanib are antifibrotic medications approved for idiopathic pulmonary fibrosis treatment by regulatory agencies and available for clinical use worldwide. These drugs have been shown to reduce the rate of decline in forced vital capacity and the risk of acute exacerbation among patients with idiopathic pulmonary fibrosis. Recent data suggest that different interstitial lung diseases with a progressive pulmonary fibrosis phenotype can share similar pathogenetic and biological pathways and could be amenable to antifibrotic therapies. Indeed, historical management strategies in interstitial lung disease have failed to identify potential treatments once progression has occurred despite available drugs. In this systematic review, we summarized data on the efficacy of pirfenidone and nintedanib in interstitial lung diseases other than idiopathic pulmonary fibrosis as well as ongoing and upcoming clinical trials. We identify two well-designed trials regarding nintedanib demonstrating the efficacy of this drug in slowing disease progression in patients with interstitial lung diseases other than idiopathic pulmonary fibrosis. On the other hand, results on the use of pirfenidone in interstitial lung diseases other than idiopathic pulmonary fibrosis should be interpreted with more caution on the basis of trial limitations. Several randomized control trials are underway to improve the quality of evidence in the interstitial lung disease field.

PMID:37175556 | DOI:10.3390/ijms24097849

Cells. 2023 Apr 26;12(9):1254. doi: 10.3390/cells12091254.

ABSTRACT

Activated M2-polarized macrophages are drivers of pulmonary fibrosis in several clinical scenarios, including Idiopathic Pulmonary Fibrosis (IPF). In this study, we investigated the effects of targeting the CD206 receptor in M2-like macrophages with a novel synthetic analogue of a naturally occurring Host Defense Peptide (HDP), RP-832c, to decrease profibrotic cytokines. RP-832c selectively binds to CD206 on M2-polarized bone marrow-derived macrophages (BMDM) in vitro, resulting in a time-dependent decrease in CD206 expression and a transient increase in M1-macrophage marker TNF-α. To elucidate the antifibrotic effects of RP-832c, we used a murine model of bleomycin (BLM)-induced early-stage pulmonary fibrosis. RP-832c significantly reduced fibrosis in a dose-dependent manner, and decreased CD206, TGF-β1, and α-SMA expression in mouse lungs. Similarly, in an established model of lung fibrosis, RP-832c significantly decreased lung fibrosis and significantly decreased inflammatory cytokines TNF-α, IL-6, IL-10, IFN-γ, CXCL1/2, and fibrosis markers TGF-β1 and MMP-13. In comparison with the FDA-approved drugs Nintedanib and Pirfenidone, RP-832c exhibited a similar reduction in fibrosis compared to Pirfenidone, and to a greater extent than Nintedanib, with no apparent toxicities observed. In summary, our findings showed that inhibiting the profibrotic alternatively activated M2-like macrophages using a novel peptide, RP-832c, could reduce BLM-induced pulmonary fibrosis in mice, warranting the therapeutic potential of this peptide for patients with pulmonary fibrosis.

PMID:37174654 | DOI:10.3390/cells12091254

BMC Complement Med Ther. 2023 May 12;23(1):155. doi: 10.1186/s12906-023-03974-1.

ABSTRACT

INTRODUCTION: In this study, we will combine the traditional Baduanjin with Yijin Jing and Wuqinxi to create an optimized Baduanjin exercise program with three different forms (vertical, sitting, and horizontal) to adapt to idiopathic pulmonary fibrosis (IPF) patients in vairous stages of the disease. The purpose of this study is to explore and compare the therapeutic effects of this multi-form Baduanjin, traditional Baduanjin, and resistance training on lung function and limb motor function in IPF patients. The goal of this study is to prove a novel optimal exercise prescription strategy of Baduanjin exercise for improving and protecting lung function in IPF patients.

METHODS/DESIGN: A single-blind and randomized controlled trial is used to conduct this study, while the randomization list will be generated using a computerized random number generator and opaque sealed envelopes with group allocation will be prepared. It will be strictly followed to blind the outcome assessors. and until the experiment's conclusion, participants won't know which group they are enrolled in. Patients between the ages of 35 and 80 who have stable diseases and have not regularly practiced Baduanjin exercise in the past will be included. They are divvied up into the following five groups at random: (1) The conventional care group (control group, CG), (2) The traditional Baduanjin exercise group (TG), (3) The modified Baduanjin exercise group (IG), (4) The resistance exercise group (RG) (5) The modified Baduanjin exercise combined with resistance exercise group (IRG). Those CG participants only received the usual treatment, while TC, IG, and RG participants exercised 1 h twice a day for 3 months. MRG participants will have a 3-month intervention with 1 h of Modified Baduanjin Exercise and 1 H of Resistance Training for each day. Every week, all groups underwent will supervis one-day training, with the exception of the control group. The Pulmonary Function Testing (PFT), HRCT, and 6MWT are the main outcome variables. The St. George Respiratory Questionnaire and mMRC are used as secondary outcome measures.

DISCUSSION: This study may produce a new Baduanjin exercise prescription that is user-friendly, simple to execute, more targeted, and adaptable. Because it consists of three forms, including vertical, sitting, and horizontal, it is more adaptable to the various disease stages and actual situations of IPF patients and may compensate for the shortcomings of conventional pulmonary rehabilitation and traditional Baduanjin.

TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055559 . Registered on 12 January 2022.

PMID:37173702 | DOI:10.1186/s12906-023-03974-1