Idiopathic pulmonary fibrosis: unmasking cryptogenic environmental factors

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown origin that is associated with high morbidity and mortality. In this perspective, we briefly review the current understanding of the pathophysiology of IPF and the importance of environmental triggers as a precipitant of disease. We discuss occult intrinsic and extrinsic environmental factors that affect the lung microenvironment and may contribute to the development and progression of disease. The clinical implications of this framework need to be further elucidated, because prompt identification and elimination of occult exposures may represent a novel treatment modality.

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Complications in Idiopathic Pulmonary Fibrosis: Focus on Their Clinical and Radiological Features

Diagnostics ◽

10.3390/diagnostics10070450 ◽

2020 ◽

Vol 10 (7) ◽

pp. 450

Author(s):

Federica Galioto ◽

Stefano Palmucci ◽

Giovanna M. Astuti ◽

Ada Vancheri ◽

Giulio Distefano ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Disease ◽

Integrated Approach ◽

Correct Treatment ◽

Radiological Features ◽

Palliative Care Services ◽

Pictorial Essay ◽

Personalized Approach ◽

Fibrotic Lung Disease

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease with uncertain origins and pathogenesis; it represents the most common interstitial lung disease (ILD), associated with a pathological pattern of usual interstitial pneumonitis (UIP). This disease has a poor prognosis, having the most lethal prognosis among ILDs. In fact, the progressive fibrosis related to IPF could lead to the development of complications, such as acute exacerbation, lung cancer, infections, pneumothorax and pulmonary hypertension. Pneumologists, radiologists and pathologists play a key role in the identification of IPF disease, and in the characterization of its complications—which unfortunately increase disease mortality and reduce overall survival. The early identification of these complications is very important, and requires an integrated approach among specialists, in order to plane the correct treatment. In some cases, the degree of severity of patients having IPF complications may require a personalized approach, based on palliative care services. Therefore, in this paper, we have focused on clinical and radiological features of the complications that occurred in our IPF patients, providing a comprehensive and accurate pictorial essay for clinicians, radiologists and surgeons involved in their management.

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The Its Not JUST Idiopathic pulmonary fibrosis Study (INJUSTIS): description of the protocol for a multicentre prospective observational cohort study identifying biomarkers of progressive fibrotic lung disease

BMJ Open Respiratory Research ◽

10.1136/bmjresp-2019-000439 ◽

2019 ◽

Vol 6 (1) ◽

pp. e000439 ◽

Cited By ~ 2

Author(s):

Fasihul Khan ◽

Iain Stewart ◽

Lucy Howard ◽

Tricia M McKeever ◽

Steve Jones ◽

...

Keyword(s):

Cohort Study ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Disease ◽

Molecular Mechanisms ◽

Observational Cohort Study ◽

Prospective Observational Cohort Study ◽

Ethical Approval ◽

Observational Cohort ◽

Fibrotic Lung Disease

IntroductionThe Its Not JUST Idiopathic pulmonary fibrosis Study (INJUSTIS) is a multicentre, prospective, observational cohort study. The aims of this study are to identify genetic, serum and other biomarkers that may identify specific molecular mechanisms, reflecting disease endotypes that are shared among patients with progressive pulmonary fibrosis regardless of aetiology. Furthermore, it is anticipated that these biomarkers will help predict fibrotic activity that may identify patterns of disease behaviour with greater accuracy than current clinical phenotyping.Methods and analysis200 participants with the multidisciplinary team confirmed fibrotic lung disease (50 each of rheumatoid-interstitial lung disease (ILD), asbestosis, chronic hypersensitivity pneumonitis and unclassifiable ILD) and 50 idiopathic pulmonary fibrosis participants, recruited as positive controls, will be followed up for 2 years. Participants will have blood samples, lung function tests, quality of life questionnaires and a subgroup will be offered bronchoscopy. Participants will also be given the option of undertaking blinded home handheld spirometry for the first 3 months of the study. The primary end point will be identification of a biomarker that predicts disease progression, defined as 10% relative change in forced vital capacity (FVC) or death at 12 months.Ethics and disseminationThe trial has received ethical approval from the National Research Ethics Committee Nottingham (18/EM/0139). All participants must provide written informed consent. The trial will be overseen by the INJUSTIS steering group that will include a patient representative, and an independent chairperson. The results from this study will be submitted for publication in peer-reviewed journals and disseminated at regional and national conferences.Trial registration numberNCT03670576.

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Diagnosing fibrotic lung disease: When is high-resolution computed tomography sufficient to make a diagnosis of idiopathic pulmonary fibrosis?

Respirology ◽

10.1111/j.1440-1843.2009.01626.x ◽

2009 ◽

Vol 14 (7) ◽

pp. 934-939 ◽

Cited By ~ 41

Author(s):

Shelley L. SCHMIDT ◽

Baskaran SUNDARAM ◽

Kevin R. FLAHERTY

Keyword(s):

Computed Tomography ◽

High Resolution ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Disease ◽

High Resolution Computed Tomography ◽

Fibrotic Lung Disease

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Causes of Pulmonary Fibrosis in the Elderly

Medical Sciences ◽

10.3390/medsci6030058 ◽

2018 ◽

Vol 6 (3) ◽

pp. 58 ◽

Cited By ~ 2

Author(s):

Cecilia López-Ramírez ◽

Lionel Suarez Valdivia ◽

Jose Rodríguez Portal

Keyword(s):

Prognostic Factors ◽

Environmental Factors ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Elderly Population ◽

The Elderly ◽

Epidemiological Studies ◽

Epigenetic Changes ◽

Telomere Attrition ◽

Inflammatory Infiltrates

Idiopathic pulmonary fibrosis (IPF) is the most common and most lethal type of idiopathic interstitial pneumonia. It is a chronic, aging-associated lung disease characterized by fibrotic foci and inflammatory infiltrates, with no cure and very limited therapeutic options. Although its etiology is unknown, several pathogenic pathways have been described that could explain this process, involving aging, environmental factors, genomic instability, loss of proteostasis, telomere attrition, epigenetic changes, mitochondrial dysfunction, cell senescence, and altered intercellular communication. One of the main prognostic factors for the development of IPF in broad epidemiological studies is age. The incidence increases with age, making this a disease that predominantly affects the elderly population, being exceptional under 45 years of age. However, the degree to which each of these mechanisms is involved in the etiology of the uncontrolled fibrogenesis that defines IPF is still unknown. Clarifying these questions is crucial to the development of points of intervention in the pathogenesis of the disease. This review briefly summarizes what is known about each possible etiological factor, and the questions that most urgently need to be addressed.

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Association of circulating cell-free double-stranded DNA and metabolic derangements in idiopathic pulmonary fibrosis

Thorax ◽

10.1136/thoraxjnl-2021-217315 ◽

2021 ◽

pp. thoraxjnl-2021-217315

Author(s):

William Whalen ◽

Mustafa Buyukozkan ◽

Bethany Moore ◽

Jong-Seok Moon ◽

Charles S Dela Cruz ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Fibrosis ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Rapid Progression ◽

Healthy Controls ◽

Double Stranded Dna ◽

Slow Progressors ◽

Progression Of Disease

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with unclear aetiology and poorly understood pathophysiology. Although plasma levels of circulating cell-free DNA (ccf-DNA) and metabolomic changes have been reported in IPF, the associations between ccf-DNA levels and metabolic derangements in lung fibrosis are unclear. Here, we demonstrate that ccf-double-stranded DNA (dsDNA) is increased in patients with IPF with rapid progression of disease compared with slow progressors and healthy controls and that ccf-dsDNA associates with amino acid metabolism, energy metabolism and lipid metabolism pathways in patients with IPF.

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PTX3 Regulation of Inflammation, Hemostatic Response, Tissue Repair, and Resolution of Fibrosis Favors a Role in Limiting Idiopathic Pulmonary Fibrosis

Frontiers in Immunology ◽

10.3389/fimmu.2021.676702 ◽

2021 ◽

Vol 12 ◽

Author(s):

Andrea Doni ◽

Alberto Mantovani ◽

Barbara Bottazzi ◽

Remo Castro Russo

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Fibrosis ◽

Tissue Repair ◽

Therapeutic Potential ◽

Tissue Injury ◽

Life Quality ◽

Unknown Origin ◽

Protective Role

PTX3 is a soluble pattern recognition molecule (PRM) belonging to the humoral innate immune system, rapidly produced at inflammatory sites by phagocytes and stromal cells in response to infection or tissue injury. PTX3 interacts with microbial moieties and selected pathogens, with molecules of the complement and hemostatic systems, and with extracellular matrix (ECM) components. In wound sites, PTX3 interacts with fibrin and plasminogen and favors a timely removal of fibrin-rich ECM for an efficient tissue repair. Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown origin, associated with excessive ECM deposition affecting tissue architecture, with irreversible loss of lung function and impact on the patient’s life quality. Maccarinelli et al. recently demonstrated a protective role of PTX3 using the bleomycin (BLM)-induced experimental model of lung fibrosis, in line with the reported role of PTX3 in tissue repair. However, the mechanisms and therapeutic potential of PTX3 in IPF remained to be investigated. Herein, we provide new insights on the possible role of PTX3 in the development of IPF and BLM-induced lung fibrosis. In mice, PTX3-deficiency was associated with worsening of the disease and with impaired fibrin removal and subsequently increased collagen deposition. In IPF patients, microarray data indicated a down-regulation of PTX3 expression, thus suggesting a potential rational underlying the development of disease. Therefore, we provide new insights for considering PTX3 as a possible target molecule underlying therapeutic intervention in IPF.

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Idiopathic pulmonary fibrosis: the radiologist’s role in making the diagnosis

British Journal of Radiology ◽

10.1259/bjr.20181003 ◽

2019 ◽

Vol 92 (1099) ◽

pp. 20181003 ◽

Cited By ~ 2

Author(s):

Michael P. Mohning ◽

John Caleb Richards ◽

Tristan J. Huie

Keyword(s):

Differential Diagnosis ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Disease ◽

Lung Biopsy ◽

Critical Role ◽

Pattern Identification ◽

Diagnostic Process ◽

Imaging Features ◽

Fibrotic Lung Disease

Radiologists have a critical role in the evaluation and diagnosis of suspected idiopathic pulmonary fibrosis (IPF). Accurate pattern identification on imaging is key in the multidisciplinary diagnostic process and frequently obviates the need for a surgical lung biopsy. In this review, we describe the clinical and imaging features of IPF in the context of recently revised international guidelines; contrast findings in other diseases that may inform differential diagnosis of fibrotic lung disease; and highlight common complications associated with pulmonary fibrosis.

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