Biomedicines. 2022 Apr 28;10(5):1017. doi: 10.3390/biomedicines10051017.

ABSTRACT

Asthma is a heterogeneous pulmonary disorder, the progression and chronization of which leads to airway remodeling and fibrogenesis. To understand the molecular mechanisms of pulmonary fibrosis development, key genes forming the asthma-specific regulome and involved in lung fibrosis formation were revealed using a comprehensive bioinformatics analysis. The bioinformatics data were validated using a murine model of ovalbumin (OVA)-induced asthma and post-asthmatic fibrosis. The performed analysis revealed a range of well-known pro-fibrotic markers (Cat, Ccl2, Ccl4, Ccr2, Col1a1, Cxcl12, Igf1, Muc5ac/Muc5b, Spp1, Timp1) and a set of novel genes (C3, C3ar1, Col4a1, Col4a2, Cyp2e1, Fn1, Thbs1, Tyrobp) mediating fibrotic changes in lungs already at the stage of acute/subacute asthma-driven inflammation. The validation of genes related to non-allergic bleomycin-induced pulmonary fibrosis on asthmatic/fibrotic lungs allowed us to identify new universal genes (Col4a1 and Col4a2) associated with the development of lung fibrosis regardless of its etiology. The similarities revealed in the expression profiles of nodal fibrotic genes between asthma-driven fibrosis in mice and nascent idiopathic pulmonary fibrosis in humans suggest a tight association of identified genes with the early stages of airway remodeling and can be considered as promising predictors and early markers of pulmonary fibrosis.

PMID:35625754 | DOI:10.3390/biomedicines10051017

Biomolecules. 2022 May 22;12(5):728. doi: 10.3390/biom12050728.

ABSTRACT

(1) Background: Abnormal repair after alveolar epithelial injury drives the progression of idiopathic pulmonary fibrosis (IPF). The maintenance of epithelial integrity is based on the self-renewal and differentiation of alveolar type 2 (AT2) cells, which require sufficient energy. However, the role of glutamine metabolism in the maintenance of the alveolar epithelium remains unclear. In this study, we investigated the role of glutamine metabolism in AT2 cells of patients with IPF and in mice with bleomycin-induced fibrosis. (2) Methods: Single-cell RNA sequencing (scRNA-seq), transcriptome, and metabolomics analyses were conducted to investigate the changes in the glutamine metabolic pathway during pulmonary fibrosis. Metabolic inhibitors were used to stimulate AT2 cells to block glutamine metabolism. Regeneration of AT2 cells was detected using bleomycin-induced mouse lung fibrosis and organoid models. (3) Results: Single-cell analysis showed that the expression levels of catalytic enzymes responsible for glutamine catabolism were downregulated (p < 0.001) in AT2 cells of patients with IPF, suggesting the accumulation of unusable glutamine. Combined analysis of the transcriptome (p < 0.05) and metabolome (p < 0.001) revealed similar changes in glutamine metabolism in bleomycin-induced pulmonary fibrosis in mice. Mechanistically, inhibition of the key enzymes involved in glucose metabolism, glutaminase-1 (GLS1) and glutamic-pyruvate transaminase-2 (GPT2) leads to reduced proliferation (p < 0.01) and differentiation (p < 0.01) of AT2 cells. (4) Conclusions: Glutamine metabolism is required for alveolar epithelial regeneration during lung injury.

PMID:35625656 | DOI:10.3390/biom12050728

Respir Res. 2022 May 27;23(1):135. doi: 10.1186/s12931-022-02033-6.

ABSTRACT

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) frequently have multiple comorbidities, which may influence survival but go under-recognised in clinical practice. We therefore report comorbidity, antifibrotic treatment use and survival of patients with IPF observed in the multi-national EMPIRE registry.

METHODS: For this prospective IPF cohort, demographics, comorbidities, survival and causes of death were analysed. Comorbidities were noted by the treating physician based on the patient's past medical history or as reported during follow-up. Comorbidities were defined as prevalent when noted at enrolment, or as incident when recorded during follow-up. Survival was analysed by Kaplan-Meier estimates, log-rank test, and Cox proportional hazards models. Hazard ratios (HR) were adjusted for gender, age, smoking status and FVC at enrolment.

RESULTS: A population of 3,580 patients with IPF from 11 Central and Eastern European countries was followed every 6 months for up to 6 years. At enrolment, 91.3% of patients reported at least one comorbidity, whereas more than one-third (37.8%) reported four or more comorbidities. Five-year survival was 53.7% in patients with no prevalent comorbidities, whereas it was 48.4%, 47.0%, 43.8% and 41.1% in patients with 1, 2, 3 and ≥ 4 comorbidities, respectively. The presence of multiple comorbidities at enrolment was associated with significantly worse survival (log-rank test P = 0.007). Adjusted HRs indicate that risk of death was increased by 44% in patients with IPF reporting ≥ 4 comorbidities at baseline compared with no comorbidity (P = 0.021). The relationship between number of comorbidities and decreased survival was also seen in patients receiving antifibrotic treatment (63% of all patients; log-rank test P < 0.001). Comorbidity as cause of death was identified in at least 26.1% of deaths.

CONCLUSIONS: The majority of patients with IPF demonstrate comorbidities, and many have comorbidity-related deaths. Increasing numbers of comorbidities are associated with worse survival; and this pattern is also present in patients receiving antifibrotic therapy.

PMID:35624513 | DOI:10.1186/s12931-022-02033-6

Clin Nutr ESPEN. 2022 Jun;49:295-300. doi: 10.1016/j.clnesp.2022.03.035. Epub 2022 Apr 6.

ABSTRACT

BACKGROUND & AIMS: Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a growing prevalence. We aimed to evaluate the effects of co-supplementation with vitamins C, E, and D on respiratory, inflammatory, and oxidative stress outcomes in IPF patients.

METHODS: Thirty-three patients participated in this quasi-experimental study and were supplemented with vitamins E, C, and D with 200 IU/daily, 250 mg/every other day and 50000 IU/Weekly, respectively for 12 weeks. Anthropometric indices, dietary recall, physical activity, Saint George questionnaire were assessed along with the biochemical measures of inflammation and oxidative stress, and respiratory parameters. Data were analyzed by SPSS version 21, and P-value ≤ 0.05 was considered significant.

RESULTS: Results of spirometry and plethysmography tests showed a significant increase in FEV1 (P-value = 0.016), IRV (P-value = 0.001), RV (P-value = 0.002) and TLC (P-value = 0.003). But no significant change was observed in FVC, VC, FEV1/FVC, and ERV. We also found that ESR, hs-CRP, TGFβ, and PrC remarkably reduced after the supplementation (P-value ≤ 0.05), while the GPx level remained unchanged.

CONCLUSIONS: It is concluded that three months of supplementation with a combination of D, C, and E vitamins in IPF patients may positively affect the respiratory function and alleviate the inflammation and oxidative stress.

PMID:35623829 | DOI:10.1016/j.clnesp.2022.03.035

Toxicol Appl Pharmacol. 2022 May 23:116070. doi: 10.1016/j.taap.2022.116070. Online ahead of print.

ABSTRACT

Inflammation and resolution are dynamic processes comprised of inflammatory activation and neutrophil influx, followed by mediator catabolism and efferocytosis. These critical pathways ensure a return to homeostasis and promote repair. Over the past decade research has shown that diverse mediators play a role in the active process of resolution. Specialized pro-resolving mediators (SPMs), biosynthesized from fatty acids, are released during inflammation to facilitate resolution and are deficient in a variety of lung disorders. Failed resolution results in remodeling and cellular deposition through pro-fibrotic myofibroblast expansion that irreversibly narrows the airways and worsens lung function. Recent studies indicate environmental exposures may perturb and deregulate critical resolution pathways. Environmental xenobiotics induce lung inflammation and generate reactive metabolites that promote oxidative stress, injuring the respiratory mucosa and impairing gas-exchange. This warrants recognition of xenobiotic associated molecular patterns (XAMPs) as new signals in the field of inflammation biology, as many environmental chemicals generate free radicals capable of initiating the inflammatory response. Recent studies suggest that unresolved, persistent inflammation impacts both resolution pathways and endogenous regulatory mediators, compromising lung function, which over time can progress to chronic lung disease. Chronic ozone (O3) exposure overwhelms successful resolution, and in susceptible individuals promotes asthma onset. The industrial contaminant cadmium (Cd) bioaccumulates in the lung to impair resolution, and recurrent inflammation can result in chronic obstructive pulmonary disease (COPD). Persistent particulate matter (PM) exposure increases systemic cardiopulmonary inflammation, which reduces lung function and can exacerbate asthma, COPD, and idiopathic pulmonary fibrosis (IPF). While recurrent inflammation underlies environmentally induced pulmonary morbidity and may drive the disease process, our understanding of inflammation resolution in this context is limited. This review aims to explore inflammation resolution biology and its role in chronic environmental lung disease(s).

PMID:35618031 | DOI:10.1016/j.taap.2022.116070

ERJ Open Res. 2022 May 23;8(2):00640-2021. doi: 10.1183/23120541.00640-2021. eCollection 2022 Apr.

ABSTRACT

This article provides an overview of scientific highlights in the field of interstitial lung disease (ILD), presented at the virtual European Respiratory Society Congress 2021. A broad range of topics was discussed this year, ranging from translational and genetic aspects to novel innovations with the potential to improve the patient pathway. Early Career Members summarise a selection of interesting findings from different congress sessions, together with the leadership of Assembly 12 - Interstitial Lung Disease.

PMID:35615418 | PMC:PMC9124869 | DOI:10.1183/23120541.00640-2021

Sci Rep. 2022 May 25;12(1):8817. doi: 10.1038/s41598-022-12693-5.

ABSTRACT

The revised definition of acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) was proposed in 2016, but changes in the incidence and impact on prognosis of the re-defined AE compared to those of the previous definition remain unclear. Clinical data of 445 patients with IPF (biopsy proven cases: 165) were retrospectively reviewed. The median follow-up period was 36.8 months and 17.5% (n = 78) experienced AE more than once. The 1- and 3-year incidence rates of AE were 6.7% and 16.6%, respectively, and idiopathic AE accounted for 82.1% of AE. Older age, lower diffusing capacity of the lung for carbon monoxide and 10% relative decline in forced vital capacity for 6 months were independently associated with AE. The in-hospital mortality rate following AE was 29.5%. In the multivariable analysis, AE was independently associated with poor prognosis in patients with IPF. Compared to the old definition, the revised definition relatively increased the incidence of AE by 20.4% and decreased the in-hospital mortality by 10.1%. Our results suggest that the revised definition affects approximately 20% increase in the incidences and 10% reduction in the in-hospital mortality of AE defined by the past definition.

PMID:35614114 | DOI:10.1038/s41598-022-12693-5

Am J Respir Cell Mol Biol. 2022 May 25. doi: 10.1165/rcmb.2022-0037MA. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with no curative pharmacological treatment. Current preclinical models fail to accurately reproduce human pathophysiology and are therefore poor predictors of clinical outcomes. Here, we investigated whether the chick embryo chorioallantoic membrane (CAM) assay supports the implantation of xenografts derived from IPF lung tissue and primary IPF lung fibroblasts and can be used to evaluate the efficacy of antifibrotic drugs. We demonstrate that IPF xenografts maintain their integrity and are perfused with chick embryo blood. Size measurements indicate that the xenografts amplify on the CAM, and Ki67 and pro-collagen type I immunohistochemical staining highlight the presence of proliferative and functional cells in the xenografts. Moreover, the IPF phenotype and immune microenvironment of lung tissues are retained when cultivated on the CAM and the fibroblast xenografts mimic invasive IPF fibroblastic foci. Daily treatments of the xenografts with nintedanib and PBI-4050 significantly reduce their size, fibrosis-associated gene expression, and collagen deposition. Similar effects are found with GLPG1205 and fenofibric acid, two drugs that target the immune microenvironment. Our CAM-IPF model represents the first in vivo model of IPF that uses human lung tissue. This rapid and cost-effective assay could become a valuable tool for predicting the efficacy of antifibrotic drug candidates for IPF.

PMID:35612953 | DOI:10.1165/rcmb.2022-0037MA

Am J Respir Crit Care Med. 2022 May 25. doi: 10.1164/rccm.202204-0756LE. Online ahead of print.

NO ABSTRACT

PMID:35612928 | DOI:10.1164/rccm.202204-0756LE

Am J Respir Crit Care Med. 2022 May 25. doi: 10.1164/rccm.202205-0877LE. Online ahead of print.

NO ABSTRACT

PMID:35612926 | DOI:10.1164/rccm.202205-0877LE

Am J Respir Crit Care Med. 2022 May 25. doi: 10.1164/rccm.202205-0850LE. Online ahead of print.

NO ABSTRACT

PMID:35612921 | DOI:10.1164/rccm.202205-0850LE

Bioengineered. 2022 May;13(5):12772-12782. doi: 10.1080/21655979.2022.2073145.

ABSTRACT

Cardiovascular risk factors have attracted increasing attention in recent years with the acceleration of population aging, amongst which cardiac hypertrophy is the initiating link to heart failure. Pirfenidone is a promising agent for the treatment of idiopathic pulmonary fibrosis and has recently proven to exert inhibitory effects on the inflammatory response. This study proposes to explore the potential pharmacological action of Pirfenidone in treating cardiac hypertrophy in a rodent model. Four groups of mice were used in the present study: the control, ISO (5 mg/kg/day) for 7 days, Pirfenidone (200 mg/kg/day) for 14 days, and Spironolactone (SPI) (200 mg/kg/day) for 14 days groups. Increased heart weight index, left ventricle (LV) weight index, LV wall thickness, declined LV volume, and elevated serum levels of CK-MB, AST, and LDH were observed in ISO-challenged mice, all of which were dramatically reversed by the administration of Pirfenidone or SPI. Furthermore, an elevated cross-sectional area of cardiomyocytes in the wheat germ agglutinin (WGA) staining of heart cross-sections, upregulated atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), β Myosin Heavy Chain (β-MHC), and excessively released tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in cardiac tissues were observed in the ISO group but greatly alleviated by Pirfenidone or SPI. Lastly, the promoted expression levels of p-JAK-2/JAK-2 and p-STAT3/STAT-3 in the cardiac tissues of ISO-challenged mice were significantly repressed by Pirfenidone or SPI. Collectively, our data reveals a therapeutic property of Pirfenidone on ISO-induced cardiac hypertrophy in mice.

PMID:35609321 | DOI:10.1080/21655979.2022.2073145

Am J Respir Cell Mol Biol. 2022 May 24. doi: 10.1165/rcmb.2021-0554OC. Online ahead of print.

ABSTRACT

We previously identified a novel molecular subtype of idiopathic pulmonary fibrosis (IPF) defined by increased expression of cilium-associated genes, airway mucin gene MUC5B, and KRT5 marker of basal cell airway progenitors. Here we show the association of MUC5B and cilia gene expression in human IPF airway epithelial cells, providing further rationale for examining the role of cilium genes in pathogenesis of IPF. We demonstrate increased multiciliogenesis and changes in motile cilia structure of multiciliated cells both in IPF and bleomycin lung fibrosis model. Importantly, conditional deletion of a cilium gene, Intraflagellar Transport 88 (Ift88), in Krt5 basal cells reduces Krt5 pod formation and lung fibrosis whereas no changes are observed in Ift88 conditional deletion in club cell progenitors. Our findings indicate that aberrant injury-activated primary ciliogenesis and Hedgehog signaling may play a causative role in Krt5 pod formation, which leads to aberrant multiciliogenesis and lung fibrosis. This implies that modulating cilium gene expression in Krt5 cell progenitors is a potential therapeutic target for IPF.

PMID:35608953 | DOI:10.1165/rcmb.2021-0554OC

J Pathol. 2022 May 24. doi: 10.1002/path.5971. Online ahead of print.

ABSTRACT

The human lung is a relatively quiescent organ in the normal healthy state but contains stem/progenitor cells that contribute to normal tissue maintenance and either repair or remodeling in response to injury and disease. Maintenance or repair lead to proper restoration of functional lung tissue and maintenance of physiological functions, with remodeling resulting in altered structure and function that is typically associated with disease. Knowledge of cell types contributing to lung tissue maintenance and repair/remodeling have largely relied on mouse models of injury-repair and lineage tracing of local progenitors. Therefore, many of the functional alterations underlying remodeling in human lung disease, have remained poorly defined. However, the advent of advanced genomics approaches to define the molecular phenotype of lung cells at single cell resolution has paved the way for rapid advances in our understanding of cell types present within the normal human lung and changes that accompany disease. Here we summarize recent advances in our understanding of disease-related changes in the molecular phenotype of human lung epithelium that have emerged from single-cell transcriptomic studies. We focus attention on emerging concepts of epithelial transitional states that characterize the pathological remodeling that accompanies chronic lung diseases, including idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, cystic fibrosis, and asthma. Concepts arising from these studies are actively evolving and require corroborative studies to improve our understanding of disease mechanisms. Whenever possible we highlight opportunities for providing a unified nomenclature in this rapidly advancing field of research. This article is protected by copyright. All rights reserved.

PMID:35608561 | DOI:10.1002/path.5971

BMC Pulm Med. 2022 May 23;22(1):203. doi: 10.1186/s12890-022-02000-3.

ABSTRACT

BACKGROUND: The serum creatinine/cystatin C (Cr/CysC) ratio has attracted attention as a marker for sarcopenia, but has not been studied in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to confirm the utility of the serum Cr/CysC ratio in predicting sarcopenia and investigate its clinical relevance.

METHODS: This cross-sectional pilot study prospectively enrolled patients with stable IPF. IPF was diagnosed through multidisciplinary discussions according to the 2018 international guidelines, and sarcopenia was diagnosed according to the 2019 consensus report of the Asian Working Group for Sarcopenia. Patient-reported outcomes (PROs) were evaluated using the modified Medical Research Council (mMRC) dyspnea scale, chronic obstructive pulmonary disease assessment test (CAT), and King's Brief Interstitial Lung Disease (K-BILD) questionnaire. The associations between serum Cr/CysC ratio and the presence of sarcopenia and other clinical parameters, including PROs scores, were examined.

RESULTS: The study enrolled 49 Japanese patients with IPF with a mean age of 73.0 ± 7.7 years and a mean percentage of predicted forced vital capacity of 80.4 ± 15.5%. Sarcopenia was diagnosed in 18 patients (36.7%), and the serum Cr/CysC ratio was 0.86 [0.76-0.94] (median [interquartile range]). The receiver operating characteristic curve analyses for the detection of sarcopenia according to the serum Cr/CysC showed that the area under the curve, optimal cutoff value, specificity, and sensitivity were 0.85, 0.88, 0.65, and 0.94, respectively. Sarcopenia was identified in 13% of patients with a high serum Cr/CysC ratio (≥ 0.88) and 60% of patients with a low serum Cr/CysC ratio (< 0.88) (P < 0.001). Multiple linear regression analysis showed that the serum Cr/CysC ratio was an independent predictive marker of worse PROs evaluated using mMRC (P < 0.05), CAT (P < 0.05), and K-BILD (P < 0.05).

CONCLUSIONS: This study showed that the serum Cr/CysC ratio may be a surrogate marker of sarcopenia in patients with IPF. Furthermore, it is important to pay attention to the serum Cr/CysC ratio because a lower serum Cr/CysC ratio is associated with worse PROs. Further studies are required to validate these observations to determine whether the Cr/CysC ratio can be used to detect sarcopenia in patients with IPF.

PMID:35606777 | DOI:10.1186/s12890-022-02000-3

Eur Respir J. 2022 Apr 7:2102373. doi: 10.1183/13993003.02373-2021. Online ahead of print.

NO ABSTRACT

PMID:35604813 | DOI:10.1183/13993003.02373-2021

Bioeng Transl Med. 2022 Jan 18;7(2):e10280. doi: 10.1002/btm2.10280. eCollection 2022 May.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by the infiltration of macrophages in the fibrotic region. Currently, no therapeutic strategies effectively control disease progression, and the 5-year mortality of patients after diagnosis is unacceptably high. Thus, developing an effective and safe treatment for IPF is urgently needed. The present study illustrated that methyl-CpG-binding protein 2 (MECP2), a protein responsible for the interpretation of DNA methylome-encoded information, was abnormally expressed in lung and bronchoalveolar lavage fluid samples of IPF patients and mice with onset of pulmonary fibrosis. And further studies verified that the overexpression of MECP2 occurred mainly in macrophages. Inhibition of Mecp2 expression in macrophages robustly abrogated alternatively activated macrophage (M2) polarization by regulating interferon regulatory factor 4 expression. Accordingly, cationic liposomes loading Mecp2 small interfering RNA (siRNA) were raised for the treatment of pulmonary fibrosis. It was noted that the liposomes accumulated in the fibrotic region after intratracheal injection, especially in macrophages. In addition, intratracheal administration of Mecp2 siRNA-loaded liposomes significantly reversed the established pulmonary fibrosis with few side-effects and high safety coefficients. Collectively, these results are essential not only for further understanding the DNA methylation in pathogenesis of IPF but also for providing a potent therapeutic strategy for IPF treatment in the clinic practice.

PMID:35600643 | PMC:PMC9115697 | DOI:10.1002/btm2.10280

Zhongguo Fei Ai Za Zhi. 2022 May 20;25(5):358-362. doi: 10.3779/j.issn.1009-3419.2022.102.13.

ABSTRACT

Idiopathic Pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease with unknown cause, which is closely related to lung cancer. A serious complication called Acute exacerbation of IPF (AE-IPF) is prone to occur after lung resection. It progresses rapidly without effective treatment and has a poor prognosis. A typical case of AE-IPF after lung cancer surgery was reported, and its clinical characteristics, imaging features, diagnosis and treatment were summarized. .

PMID:35599011 | DOI:10.3779/j.issn.1009-3419.2022.102.13

Respir Res. 2022 May 21;23(1):129. doi: 10.1186/s12931-022-02047-0.

ABSTRACT

BACKGROUND: Recombinant human pentraxin-2 (rhPTX-2) significantly decreased decline in percent predicted forced vital capacity (FVC) and stabilized 6-min walk distance (6MWD) in patients with idiopathic pulmonary fibrosis (IPF) during the 28-week, placebo-controlled, randomized period of the Phase II PRM-151-202 study. Interim (76-week) data from the open-label extension (OLE) demonstrated sustained safety and efficacy with rhPTX-2 treatment. Here, we present the entire long-term OLE safety and efficacy data to 128 weeks.

METHODS: Patients who completed the randomized PRM-151-202 study period were eligible for the OLE, during which all patients received rhPTX-2, having started rhPTX-2 (i.e., crossed from placebo) or continued rhPTX-2 after Week 28. rhPTX-2 was administered in 28-week cycles, with 10 mg/kg intravenous infusions (60 min) on Days 1, 3, and 5 in the first week of each cycle, then one infusion every 4 weeks up to Week 128. The OLE primary objective was to assess the long-term safety and tolerability of rhPTX-2. Other outcomes included FVC, 6MWD, and patient-reported outcomes (descriptive analysis).

RESULTS: All 111 patients who completed the randomized period entered the OLE (n = 37 started rhPTX-2; n = 74 continued rhPTX-2); 57 (51.4%) completed to Week 128. The treatment-emergent adverse event (TEAE) profile was consistent with the randomized period, with the majority of TEAEs graded mild or moderate. Serious TEAEs occurred in 47 patients (42.3%), most frequently IPF (n = 11; 9.9%), pneumonia (n = 7; 6.3%), and acute respiratory failure (n = 3; 2.7%). Three patients underwent lung transplantation. Most serious TEAEs (and all 14 fatal events) were considered unrelated to rhPTX-2 treatment. For patients starting vs continuing rhPTX-2, mean (95% confidence interval) changes from baseline to Week 128 were, respectively, - 6.2% (- 7.7; - 4.6) and - 5.7% (- 8.0; - 3.3) for percent predicted FVC and - 36.3 m (- 65.8; - 6.9) and - 28.9 m (- 54.3; - 3.6) for 6MWD; however, conclusions were limited by patient numbers at Week 128.

CONCLUSIONS: Long-term treatment (up to 128 weeks) with rhPTX-2 was well tolerated in patients with IPF, with no new safety signals emerging in the OLE. The limited efficacy data over 128 weeks may suggest a trend towards a treatment effect. Trial registration NCT02550873; EudraCT 2014-004782-24.

PMID:35597980 | DOI:10.1186/s12931-022-02047-0

Sci Rep. 2022 May 20;12(1):8564. doi: 10.1038/s41598-022-12399-8.

ABSTRACT

Disease progression (DP) is an important parameter for the prognosis of idiopathic pulmonary fibrosis (IPF). This study aimed to evaluate the baseline serum biomarkers for predicting the DP in IPF. Seventy-four patients who were diagnosed with IPF and had their serum Krebs von den Lungen-6 (KL-6) and monocyte count, which might be associated with prognosis of IPF, checked more than twice were included. KL-6 ≥ 1000 U/mL and monocyte ≥ 600/μL were arbitrarily set as the cut-off values for DP. The DP was defined as a 10% reduction in forced vital capacity, a 15% reduction in diffusing capacity of the lung for carbon monoxide relative to the baseline, or disease-related mortality. Of the 74 patients, 18 (24.3%) were defined as having DP. The baseline KL-6 level was significantly increased in the DP group compared to the stable disease group (median, 1228.0 U/mL vs. 605.5 U/mL, P = 0.019). Multivariate Cox analyses demonstrated that a high KL-6 level (KL-6 ≥ 1000 U/mL; hazard ratio, 2.761 or 2.845; P = 0.040 or 0.045) was independently associated with DP in each model. The baseline serum KL-6 level might be a useful biomarker for DP in IPF.

PMID:35595812 | DOI:10.1038/s41598-022-12399-8