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

Occup Environ Med. 2023 Jun;80(6):e1. doi: 10.1136/oemed-2022-108404corr1.

NO ABSTRACT

PMID:37172959 | DOI:10.1136/oemed-2022-108404corr1

Medicine (Baltimore). 2023 May 12;102(19):e33722. doi: 10.1097/MD.0000000000033722.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a debilitating condition, with a life expectancy of 2 to 5 years after diagnosis. Pirfenidone is a drug that has been shown to reduce the decline in forced vital capacity (FVC). We sought to identify whether different patterns on high-resolution computed tomography (HRCT) have different clinical effects through a retrospective comparison of baseline values and changes in pulmonary function tests (PFTs) after treatment with pirfenidone. We retrospectively analyzed data from IPF patients treated with pirfenidone at Nanjing Drum Tower Hospital in Jiangsu Province, China. According to the HRCT pattern, the patients were divided into usual interstitial pneumonitis (UIP) and possible UIP groups. Baseline clinical characteristics and changes every 6 months in the PFTs during the follow-up period were compared between the 2 groups. A total of 65 consecutive patients were enrolled. According to the HRCT pattern, patients were clustered into the UIP group (n = 46) and possible UIP group (n = 19). No difference was observed in the baseline PFTs ratio between the 2 groups. The FVC values of the 2 groups were not significantly different at the initial treatment and at 6 and 12 months after pirfenidone treatment (P = .081, 0.099, and 0.236, respectively). The improvement in % diffusion capacity of the lung for carbon monoxide (%DLCO) was higher in the possible UIP group after 6 and 12 months of pirfenidone treatment (P = .149, 0.026, and 0.025, respectively). The annual decrease in FVC was not significantly different between the 2 groups, and the annual decrease in %DLCO in the UIP group was significantly higher than that in patients with the possible UIP type (-7.767 ± 12.797 vs 0.342 ± 20.358, P < .05). These results indicate that patients with IPF with a possible UIP pattern on HRCT showed indications of a good response to pirfenidone.

PMID:37171315 | DOI:10.1097/MD.0000000000033722

Med Sci Sports Exerc. 2023 May 12. doi: 10.1249/MSS.0000000000003208. Online ahead of print.

ABSTRACT

PURPOSE: Cerebral hypoxia may exacerbate the perception of fatigue. We previously demonstrated that exercise-related hypoxemia, a hallmark of fibrotic interstitial lung disease (f-ILD), dose-dependently impairs cerebral oxygenation in these patients. It is unknown whether normalizing cerebral oxygenation with O2 supplementation would be associated with positive changes in a relevant patient-centered outcome during exercise in f-ILD, such as improved perceived fatigue.

METHODS: Fourteen patients (12 males, 72 ± 8 years, 8 with idiopathic pulmonary fibrosis, lung diffusing capacity for carbon monoxide = 44 ± 13% predicted) performed a constant-load (60% peak work rate) cycle test to symptom limitation (Tlim) breathing medical air. Fourteen controls cycled up to Tlim of an age- and sex-matched patient. Patients repeated the test on supplemental O2 (fraction of inspired O2 = 0.41 ± 0.08) for the same duration. Near-infrared spectroscopy and the rating-of-fatigue (ROF) scale respectively assessed prefrontal cortex oxygenation and perceived fatigue.

RESULTS: Patients showed severe exertional hypoxemia (Tlim O2 saturation by pulse oximetry = 80 ± 8%); they had poorer cerebral oxygenation [e.g. oxy-deoxyhemoglobin difference (HbDiff) = -3.5 ± 4.7 (range: -17.6 to +1.9) vs + 1.9 ± 1.7 μmol from rest] and greater fatigue (ROF = 6.2 ± 2.0 vs 2.6 ± 2.3) vs controls under air (p < 0.001). Reversal of exertional hypoxemia with supplemental O2 led to improved HbDiff (+1.7 ± 2.4 μmol from rest; no longer differing from controls) and lower ROF scores (3.7 ± 1.2; p < 0.001 vs air) in patients. There was a significant correlation between O2-induced changes in HbDiff and ROF scores throughout exercise in f-ILD (rrepeated-measures correlation = -0.51; p < 0.001).

CONCLUSIONS: Supplemental O2 improved cerebral oxygenation during exercise in f-ILD, which was moderately associated with lower ratings of perceived fatigue. Reversing cerebral hypoxia with O2 supplementation may thus have positive effects on patients' disablement beyond those expected from lower ventilation and dyspnea in this patient population.

PMID:37170955 | DOI:10.1249/MSS.0000000000003208

Ter Arkh. 2023 Apr 26;95(3):230-235. doi: 10.26442/00403660.2023.03.202073.

ABSTRACT

Progressive pulmonary fibrosis is a major problem in respiratory medicine. Currently, there are no reliable biomarkers for early diagnosis of progressive pulmonary fibrosis, which leads to delayed diagnosis.

AIM: To determine the role of serum biomarkers CA-19-9 and CA-125 and the possibilities of capillaroscopy of the nail fold in the diagnosis of progressive pulmonary fibrosis.

MATERIALS AND METHODS: The study included 43 patients with interstitial changes in the lungs. Based on the presence/absence of signs of progression over the previous 12 months, patients were divided into 2 groups. All patients underwent forced spirometry, body plethysmography, diffusion test, CT, lung ultrasound, capillaroscopy of the nail fold, study of serum concentrations of CA-19-9 and CA-125.

RESULTS: In the group of patients with a progressive fibrotic phenotype of Interstitial lung diseases, a greater severity of capillaroscopic changes and a higher level of CA-19-9 were revealed. Correlation of these parameters with changes according to CT scan data (Warrick test) and lung ultrasound was shown.

CONCLUSION: The data obtained demonstrate the possibilities of non-invasive diagnosis of progressive fibrosing interstitial lung diseases and require further research and prospective follow-up to assess the diagnostic and prognostic role of the studied biomarkers, as well as to determine their place in clinical practice.

PMID:37167144 | DOI:10.26442/00403660.2023.03.202073