Am J Respir Crit Care Med. 2023 Jul 27. doi: 10.1164/rccm.202307-1174ED. Online ahead of print.

NO ABSTRACT

PMID:37499091 | DOI:10.1164/rccm.202307-1174ED

Open Respir Arch. 2022 Dec 5;5(1):100226. doi: 10.1016/j.opresp.2022.100226. eCollection 2023 Jan-Mar.

NO ABSTRACT

PMID:37497249 | PMC:PMC10369645 | DOI:10.1016/j.opresp.2022.100226

Open Respir Arch. 2022 Jan 17;4(1):100158. doi: 10.1016/j.opresp.2022.100158. eCollection 2022 Jan-Mar.

ABSTRACT

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) impacts the life of patients and their families, so it is necessary to ascertain their perception in the approach to their disease.

METHODS: Observational study by means of a specific questionnaire that includes socio-demographic and clinical variables, perception of the impact of the disease (5-point Likert scale), preferences regarding the characteristics of the medication (degree of importance/concern 1-10) and satisfaction with treatment (SATMED-Q® scale 0-100).

RESULTS: 69 individuals participated (age: 66.5 ± 7.6 years; time until diagnosis: 16.5 ± 17.4 months; diagnosis time: 49.6 ± 42.3 months). The majority state that IPF limits them physically (90%) and emotionally (75%). The most highly valued features of the treatment were: slowing down progression of the disease (7.4 ± 2.8), stabilising lung capacity (6.9 ± 2.8) and improving quality of life (6.9 ± 2.8), above stabilising/improving symptoms (6.1 ± 2.8/6.3 ± 2.8) or avoiding hospitalisation (6.6 ± 2.7). The principal factors of concern were suffering gastric disorders (7.1 ± 2.9), photosensitivity (6.6 ± 3.0) or interaction with other drugs (6.0 ± 3.0). Overall satisfaction with the current treatment scored 61.1 points, with the highest scores being for medical follow-up (79.5) and overall opinion of the medicine (74.3).

CONCLUSIONS: A study conducted in Spain on the perspective of IPF patients regarding the disease and its treatment. The results show a high level of awareness in terms of the seriousness of the disease on the part of patients, whose main concern is to slow down its progression. The information provided may help to optimise the management of IPF patients.

PMID:37497178 | PMC:PMC10369542 | DOI:10.1016/j.opresp.2022.100158

Open Respir Arch. 2023 May 8;5(2):100248. doi: 10.1016/j.opresp.2023.100248. eCollection 2023 Apr-Jun.

ABSTRACT

Diffuse interstitial lung diseases (ILD) are a heterogeneous group of respiratory disorders that are usually classified together because they have similar clinical, radiological, physiological or pathological manifestations. In the last decade there have been important scientific advances in the study of these entities, which has led to a better understanding of their pathophysiology and to the appearance of treatments that have brought about a paradigm shift in the disease. This document presents a series of questions and answers on ILD, with special emphasis on the most relevant changes in terms of pathophysiology, diagnosis, and treatment.

PMID:37496878 | PMC:PMC10369608 | DOI:10.1016/j.opresp.2023.100248

Open Respir Arch. 2021 Apr 19;3(3):100100. doi: 10.1016/j.opresp.2021.100100. eCollection 2021 Jul-Sep.

NO ABSTRACT

PMID:37496772 | PMC:PMC10369541 | DOI:10.1016/j.opresp.2021.100100

Iran J Allergy Asthma Immunol. 2023 Apr 30;22(2):190-199. doi: 10.18502/ijaai.v22i2.12680.

ABSTRACT

The pathogenesis of idiopathic pulmonary fibrosis (IPF) is quite similar to that of cancer pathogenesis, and several pathways appear to be involved in both disorders. The mammalian target of the rapamycin (mTOR) pathway harbors several established oncogenes and tumor suppressors. The same signaling molecules and growth factors, such as vascular endothelial growth factor (VEGF), contributing to cancer development and progression play a part in fibroblast proliferation, myofibroblast differentiation, and the production of extracellular matrix in IPF development as well. The expression of candidate genes acting upstream and downstream of mTORC1, as well as Vegf and low-density lipoprotein receptor related protein 1(Lrp1), was assessed using specific primers and quantitative polymerase chain reaction (qPCR) within the lung tissues of bleomycin (BLM)-induced IPF mouse models. Lung fibrosis was evaluated by histological examinations and hydroxyproline colorimetric assay. BLM-exposed mice developed lung injuries characterized by inflammatory manifestations and fibrotic features, along with higher levels of collagen and hydroxyproline. Gene expression analyses indicated a significant elevation of regulatory associated protein of mTOR (Raptor), Ras homolog enriched in brain (Rheb), S6 kinase 1, and Eukaryotic translation initiation factor 4E-binding protein 1 (4Ebp1), as well as a significant reduction of Vegfa, Tuberous sclerosis complex (Tsc2), and Lrp1; no changes were observed in the Tsc1 mRNA level. Our findings support the elevation of S6K1 and 4EBP1 in response to the TSC/RHEB/mTORC1 axis, which profoundly encourages the development and establishment of IPF and cancer. In addition, this study suggests a possible preventive role for VEGF-A and LRP1 in the development of IPF.

PMID:37496412 | DOI:10.18502/ijaai.v22i2.12680

Nat Commun. 2023 Jul 25;14(1):4476. doi: 10.1038/s41467-023-40182-4.

ABSTRACT

Supersulphides are inorganic and organic sulphides with sulphur catenation with diverse physiological functions. Their synthesis is mainly mediated by mitochondrial cysteinyl-tRNA synthetase (CARS2) that functions as a principal cysteine persulphide synthase (CPERS). Here, we identify protective functions of supersulphides in viral airway infections (influenza and COVID-19), in aged lungs and in chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF). We develop a method for breath supersulphur-omics and demonstrate that levels of exhaled supersulphides increase in people with COVID-19 infection and in a hamster model of SARS-CoV-2 infection. Lung damage and subsequent lethality that result from oxidative stress and inflammation in mouse models of COPD, IPF, and ageing were mitigated by endogenous supersulphides production by CARS2/CPERS or exogenous administration of the supersulphide donor glutathione trisulphide. We revealed a protective role of supersulphides in airways with various viral or chronic insults and demonstrated the potential of targeting supersulphides in lung disease.

PMID:37491435 | DOI:10.1038/s41467-023-40182-4

Curr Med Imaging. 2023 Jul 25. doi: 10.2174/1573405620666230725093800. Online ahead of print.

ABSTRACT

BACKGROUND: It has been reported that structure damage in the parenchymal lung disease such as idiopathic pulmonary fibrosis (IPF) is associated with high susceptibility to nontuberculous mycobacterial (NTM) infection. Radiologic features of NTM lung disease in destructive lung parenchyma can be atypical, which can cause confusion with other diseases including malignancy. Prompt and accurate identification of newly developed lesions in the follow-up computed tomography (CT) of IPF patients is challenging but crucial.

CASE REPORT: We reported a case of an NTM infection in a patient with IPF, manifested as a mass-like consolidation with cavitation on chest CT, mimicking lung cancer.

CONCLUSION: Being aware of the unusual radiologic features of NTM lung disease in IPF patients can be useful in the differential diagnosis of newly detected lesions.

PMID:37489788 | DOI:10.2174/1573405620666230725093800

Am J Respir Crit Care Med. 2023 Jul 24. doi: 10.1164/rccm.202303-0372LE. Online ahead of print.

NO ABSTRACT

PMID:37487177 | DOI:10.1164/rccm.202303-0372LE

Am J Respir Cell Mol Biol. 2023 Jul 24. doi: 10.1165/rcmb.2022-0315OC. Online ahead of print.

ABSTRACT

Idiopathic Pulmonary Fibrosis (IPF) is an interstitial lung disease characterized by progressive lung scarring and remodeling. Although treatments exist that slow disease progression, IPF is irreversible and there is no cure. Cellular senescence, a major hallmark of aging, has been implicated in IPF pathogenesis, and mitochondrial dysfunction is increasingly recognized as a driver of senescence. Adenine nucleotide translocases (ANTs) are abundant mitochondrial ATP-ADP transporters critical for regulating cell fate and maintaining mitochondrial function. We sought to determine how alterations in ANTs influence cellular senescence in pulmonary fibrosis. We found SLC25A4 (ANT1) and SLC25A5 (ANT2) expression is reduced in the lungs of IPF patients and particularly within alveolar type II (AT2) cells by single cell RNA sequencing and tissue staining. Loss of ANT1 by siRNA in lung epithelial cells resulted in increased senescence markers such as beta-galactosidase and p21 with a reduction in the NAD+/NADH ratio. Bleomycin-treated ANT1 knockdown cells also had increased senescence markers compared to bleomycin-treated control cells. Loss of ANT1 in AT2 cells resulted in a reduction in alveolar organoid growth with an increase in p21 by staining. Global loss of ANT1 resulted in worse lung fibrosis and increased senescence in the bleomycin and asbestos-induced mouse models of pulmonary fibrosis. In summary, loss of ANT1 contributes IPF pathogenesis through mitochondrial dysfunction, increased senescence and decreased AT2 cell regenerative capacity resulting in enhanced lung fibrosis. Modulation of ANTs presents a new therapeutic avenue that may alter cellular senescence pathways and limit pulmonary fibrosis.

PMID:37487137 | DOI:10.1165/rcmb.2022-0315OC

FASEB J. 2023 Aug;37(8):e23101. doi: 10.1096/fj.202301091.

ABSTRACT

G protein-coupled receptors (GPCRs) are the largest and most diverse class of signaling receptors. GPCRs regulate many functions in the human body and have earned the title of "most targeted receptors". About one-third of the commercially available drugs for various diseases target the GPCRs. Fibroblasts lay the architectural skeleton of the body, and play a key role in supporting the growth, maintenance, and repair of almost all tissues by responding to the cellular cues via diverse and intricate GPCR signaling pathways. This review discusses the dynamic architecture of the GPCRs and their intertwined signaling in pathological conditions such as idiopathic pulmonary fibrosis, cardiac fibrosis, pancreatic fibrosis, hepatic fibrosis, and cancer as opposed to the GPCR signaling of fibroblasts in physiological conditions. Understanding the dynamics of GPCR signaling in fibroblasts with disease progression can help in the recognition of the complex interplay of different GPCR subtypes in fibroblast-mediated diseases. This review highlights the importance of designing and adaptation of next-generation strategies such as GPCR-omics, focused target identification, polypharmacology, and effective personalized medicine approaches to achieve better therapeutic outcomes for fibrosis and fibrosis associated malignancies.

PMID:37486603 | DOI:10.1096/fj.202301091

Am J Physiol Cell Physiol. 2023 Jul 24. doi: 10.1152/ajpcell.00124.2023. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is an irreversible and fatal lung disease that is primarily found in the elderly population, and several studies have demonstrated that aging is the major risk factor for IPF. IPF is characterized by the presence of apoptosis-resistant, senescent fibroblasts that generate an excessively stiff extracellular matrix (ECM). The ECM profoundly affects cellular functions and tissue homeostasis, and an aberrant ECM is closely associated with the development of lung fibrosis. Aging progressively alters ECM components and is associated with the accumulation of senescent cells which promote age-related tissue dysfunction through the expression of factors linked to a senescence-associated secretary phenotype (SASP). There is growing evidence that SASP factors affect various cell behaviors and influence ECM turnover in lung tissue through autocrine and/or paracrine signaling mechanisms. Since life expectancy is increasing worldwide, it is important to elucidate how aging affects ECM dynamics and turnover via SASP and thereby promotes lung fibrosis. In this review, we will focus on the molecular properties of SASP and its regulatory mechanisms. Furthermore, the pathophysiological process of ECM remodeling by SASP factors and the influence of an altered ECM from aged lungs on the development of lung fibrosis will be highlighted. Finally, recent attempts to target ECM alteration and senescent cells to modulate fibrosis will be introduced.

PMID:37486065 | DOI:10.1152/ajpcell.00124.2023

Pathol Res Pract. 2023 Jul 14;248:154691. doi: 10.1016/j.prp.2023.154691. Online ahead of print.

ABSTRACT

The interstitial lung diseases (ILDs) are a large, heterogeneous group of several hundred generally rare pulmonary pathologies, which show injury, inflammation and/or scarring in the lung. Although the aetiology of these disorders remains largely unknown, various cellular mechanisms have an important role in pathogenesis of fibrosis on the background of occupational, environmental and genetic factors. We have tried to provide new insights into the interactions and cellular contributions, analysing the roles of various cells in the pathogenesis of idiopathic pulmonary fibrosis.

PMID:37480596 | DOI:10.1016/j.prp.2023.154691

J Rheum Dis. 2022 Apr 1;29(2):61-70. doi: 10.4078/jrd.2022.29.2.61.

ABSTRACT

Rheumatoid arthritis (RA) is a common autoimmune disease that mainly affects the joints and systemic organs, such as the skin, eyes, heart, gastrointestinal tract, and lungs. In particular, among various pulmonary involvements, interstitial lung disease (ILD) is closely related to the selection of anti-rheumatic drugs and the long-term prognosis of patients with RA. Although the exact pathogenesis of RA-ILD is not well defined, several mechanistic pathways, similar to those of idiopathic pulmonary fibrosis, have been elucidated recently. Conversely, RA-related autoantibodies, including anti-cyclic citrullinated peptide antibody, are detectable in circulation and in the lungs, even in the absence of articular symptoms. RA-ILD can also predate years before the occurrence of joint symptoms. This evidence supports the fact that local dysregulated mucosal immunity in the lung causes systemic autoimmunity, resulting in clinically evident polyarthritis of RA. Because the early diagnosis of RA-ILD is important, imaging tests, such as computed tomography and pulmonary function tests, are being used for early diagnosis, but there is no clear guideline for the early diagnosis of RA-ILD and selection of optimal disease-modifying anti-rheumatic drugs for the treatment of patients with RA with ILD. In addition, the efficacy of nintedanib, a new anti-fibrotic agent, for RA-ILD treatment, has been investigated recently. This review collectively discusses the basic and clinical aspects, such as pathogenesis, animal models, diagnosis, and treatment, of RA-ILD.

PMID:37475899 | PMC:PMC10327618 | DOI:10.4078/jrd.2022.29.2.61

Eur Respir J. 2023 Jul 20;62(1):2300732. doi: 10.1183/13993003.00732-2023. Print 2023 Jul.

NO ABSTRACT

PMID:37474154 | DOI:10.1183/13993003.00732-2023

Eur Respir J. 2023 Jul 20;62(1):2300687. doi: 10.1183/13993003.00687-2023. Print 2023 Jul.

NO ABSTRACT

PMID:37474153 | DOI:10.1183/13993003.00687-2023

Eur Respir J. 2023 Jul 20;62(1):2300995. doi: 10.1183/13993003.00995-2023. Print 2023 Jul.

ABSTRACT

Mendelian randomisation (MR) overcomes classical confounding issues that beset observational studies. “Horizontal” but not “vertical” pleiotropy can bias MR study findings but we found no evidence that it was present in our MR analysis of GORD on IPF. https://bit.ly/3Jn7aeq

PMID:37474152 | PMC:PMC10356965 | DOI:10.1183/13993003.00995-2023

Front Pharmacol. 2023 Jul 4;14:1136761. doi: 10.3389/fphar.2023.1136761. eCollection 2023.

ABSTRACT

Introduction: Pulmonary fibrosis (PF) is a severe disease that can lead to respiratory failure and even death. However, currently there is no effective treatment available for patients with PF. Mesenchymal stem cells (MSCs) have been recently shown to have therapeutic potential for PF. We analyzed the literature focused of MSCs and PF to provide a comprehensive understanding of the relationship between MSCs and PF. Methods: We searched the Web of Science Core Collection database for literature from 2002 through 2021 that involved MSCs and PF. The included studies were then analyzed using CiteSpace and VOSviewers software. Results: A total of 1,457 studies were included for analysis. Our findings demonstrated the following: 1) an increasing trend of MSC and PF research; 2) among the 54 countries/regions of author affiliations, the United States was the most frequent, and the University of Michigan (n = 64, 2.8%) was the top institution; 3) Rojas Mauricio published the most articles and PLOS ONE had the most related studies; and 4) keywords, such as idiopathic pulmonary fibrosis, mesenchymal stem cells, and systemic sclerosis, were listed more than 100 times, indicating the research trend. Other common keywords, such as inflammation, myofibroblasts, fibroblasts, aging, telomerase or telomere, and extracellular matrix demonstrate research interests in the corresponding mechanisms.1) The number of publications focused on MSCs and PF research increased during the study period; 2) Among the 54 countries/regions of author affiliations, most articles were published in the United States of America, and the University of Michigan (n = 64, 2.8%) had the largest number of publications; 3) Rojas Mauricio published the most articles and PLOS ONE had the most related studies; 4) Keywords, such as idiopathic pulmonary fibrosis, MSCs, and systemic sclerosis, were listed more than 100 times, representing a research trend. Other common keywords included inflammation, myofibroblasts, fibroblasts, aging, telomerase or telomere, and extracellular matrix. Discussion: During the past 2 decades, MSCs have been proposed to play an important role in PF treatment. An increasing amount of literature focused on MSCs and PF research has been published. Our findings provide insight into the current status and research trends in the field of MSCs and PF research during the past 2 decades, which could help researchers understand necessary research directions. In the future, more preclinical and clinical studies should be conducted in this field to support the application of MSCs in the treatment of PF.

PMID:37469875 | PMC:PMC10352497 | DOI:10.3389/fphar.2023.1136761

Front Pharmacol. 2023 Jul 4;14:1203033. doi: 10.3389/fphar.2023.1203033. eCollection 2023.

ABSTRACT

Background: Pulmonary fibrosis (PF) is a progressive lung disease characterized by fibroblast accumulation and collagen deposition, resulting in lung scarring and impaired gas exchange. Current treatments for idiopathic pulmonary fibrosis (IPF) have limited efficacy and significant side effects. Heat shock protein 27 (HSP27) has emerged as a potential therapeutic target for PF due to its involvement in fibrotic processes. However, effective HSP27 inhibitors for PF treatment are still lacking. Methods: To assess the anti-fibrotic effects of NA49, we utilized murine PF models induced by radiation (IR) or bleomycin (BLM). We administered NA49 to the PF mice and evaluated its impact on lung fibrosis progression. We also investigated the molecular mechanisms underlying NA49's effects, focusing on its inhibition of EMT-related signaling pathways. Results: In our study, we evaluated the potential of a novel HSP27 inhibitor, NA49, in preclinical models of PF. NA49 effectively suppressed PF development in radiation and bleomycin-induced PF models. It reduced fibrosis, inhibited NFkB signaling, and downregulated EMT-related molecules. Importantly, we evaluated the safety profile of NA49 by assessing its impact on DNA strand breakage. Compared to previous HSP27 inhibitors, NA49 showed lower levels of DNA damage in human lung epithelial cells, and suggests that NA49 may have reduced toxicity compared to other HSP27 inhibitors. Overall, our results demonstrate that NA49 effectively inhibits PF development in preclinical models. It reduces lung fibrosis, inhibits EMT-related signaling pathways, and exhibits improved safety profiles. These findings highlight the potential of NA49 as a promising candidate for the treatment of PF. Conclusion: NA49 exhibited significant anti-fibrotic effects, inhibiting fibrosis development and EMT-related signaling pathways. Moreover, NA49 showed improved safety profiles compared to previous HSP27 inhibitors.

PMID:37469871 | PMC:PMC10352808 | DOI:10.3389/fphar.2023.1203033

J Multidiscip Healthc. 2023 Jul 14;16:1939-1942. doi: 10.2147/JMDH.S421089. eCollection 2023.

ABSTRACT

The purpose of this cross-sectional short report study was to evaluate the perception of pulmonologist working in noninterstitial lung disease centers on challenges (COE) encountered in daily practice. Results of this survey revealed that only 40% of their patients are referred to an ILD COE, out of 69% who have access to an ILDCOE. Of these patients who were referred, the perceived benefits were rated high when it comes to having an accurate diagnosis.

PMID:37469669 | PMC:PMC10353560 | DOI:10.2147/JMDH.S421089