-
Lancet (London, England) May 2017Idiopathic pulmonary fibrosis is a prototype of chronic, progressive, and fibrotic lung disease. Healthy tissue is replaced by altered extracellular matrix and alveolar... (Review)
Review
Idiopathic pulmonary fibrosis is a prototype of chronic, progressive, and fibrotic lung disease. Healthy tissue is replaced by altered extracellular matrix and alveolar architecture is destroyed, which leads to decreased lung compliance, disrupted gas exchange, and ultimately respiratory failure and death. In less than a decade, understanding of the pathogenesis and management of this disease has been transformed, and two disease-modifying therapies have been approved, worldwide. In this Seminar, we summarise the presentation, pathophysiology, diagnosis, and treatment options available for patients with idiopathic pulmonary fibrosis. This disease has improved understanding of the mechanisms of lung fibrosis, and offers hope that similar approaches will transform the management of patients with other progressive fibrotic lung diseases.
Topics: Humans; Idiopathic Pulmonary Fibrosis
PubMed: 28365056
DOI: 10.1016/S0140-6736(17)30866-8 -
The European Respiratory Journal Mar 2023This expert group consensus statement emphasises the need for standardising the definition of progressive fibrosing interstitial lung diseases (F-ILDs), with an accurate... (Review)
Review
This expert group consensus statement emphasises the need for standardising the definition of progressive fibrosing interstitial lung diseases (F-ILDs), with an accurate initial diagnosis being of paramount importance in ensuring appropriate initial management. Equally, case-by-case decisions on monitoring and management are essential, given the varying presentations of F-ILDs and the varying rates of progression. The value of diagnostic tests in risk stratification at presentation and, separately, the importance of a logical monitoring strategy, tailored to manage the risk of progression, are also stressed. The term "progressive pulmonary fibrosis" (PPF) exactly describes the entity that clinicians often face in practice. The importance of using antifibrotic therapy early in PPF (once initial management has failed to prevent progression) is increasingly supported by evidence. Artificial intelligence software for high-resolution computed tomography analysis, although an exciting tool for the future, awaits validation. Guidance is provided on pulmonary rehabilitation, oxygen and the use of non-invasive ventilation focused specifically on the needs of ILD patients with progressive disease. PPF should be differentiated from acute deterioration due to drug-induced lung toxicity or other forms of acute exacerbations. Referral criteria for a lung transplant are discussed and applied to patient needs in severe diseases where transplantation is not realistic, either due to access limitations or transplantation contraindications. In conclusion, expert group consensus guidance is provided on the diagnosis, treatment and monitoring of F-ILDs with specific focus on the recognition of PPF and the management of pulmonary fibrosis progressing despite initial management.
Topics: Humans; Pulmonary Fibrosis; Artificial Intelligence; Disease Progression; Lung Diseases, Interstitial; Fibrosis; Idiopathic Pulmonary Fibrosis
PubMed: 36517177
DOI: 10.1183/13993003.03187-2021 -
Expert Review of Respiratory Medicine May 2017Many forms of interstitial lung disease (ILD) can progress to extensive fibrosis and respiratory failure. Idiopathic pulmonary fibrosis (IPF), which generally has a poor... (Review)
Review
Many forms of interstitial lung disease (ILD) can progress to extensive fibrosis and respiratory failure. Idiopathic pulmonary fibrosis (IPF), which generally has a poor prognosis, has been thoroughly studied over the past two decades, and many important discoveries have been made that pertain to genetic predisposition, epidemiology, disease pathogenesis, diagnosis, and management. Additionally, non-IPF forms of ILD can have radiologic and histopathologic manifestations that mimic IPF, and making an accurate diagnosis is key to providing personalized medicine to patients with pulmonary fibrosis. Areas covered: This manuscript discusses current knowledge pertaining to the genetics, epidemiology, pathogenesis, and diagnosis of pulmonary fibrosis with an emphasis on IPF. The material upon which this discussion is based was obtained from various published texts and manuscripts identified via literature searching (e.g. PubMed). Expert commentary: Many genetic variants have been identified that are associated with risk of developing pulmonary fibrosis, and an improved understanding of the influence of both genomic and epigenomic factors in the development of pulmonary fibrosis is rapidly evolving. Because many forms of fibrosing ILD can have similar radiologic and histopathologic patterns yet have different responses to therapeutic interventions, making an accurate diagnosis of specific forms of pulmonary fibrosis is increasingly important.
Topics: Humans; Pulmonary Fibrosis
PubMed: 28345383
DOI: 10.1080/17476348.2017.1312346 -
Trends in Molecular Medicine Dec 2023Pulmonary fibrosis (PF) encompasses a spectrum of chronic lung diseases that progressively impact the interstitium, resulting in compromised gas exchange,... (Review)
Review
Pulmonary fibrosis (PF) encompasses a spectrum of chronic lung diseases that progressively impact the interstitium, resulting in compromised gas exchange, breathlessness, diminished quality of life (QoL), and ultimately respiratory failure and mortality. Various diseases can cause PF, with their underlying causes primarily affecting the lung interstitium, leading to their referral as interstitial lung diseases (ILDs). The current understanding is that PF arises from abnormal wound healing processes triggered by various factors specific to each disease, leading to excessive inflammation and fibrosis. While significant progress has been made in understanding the molecular mechanisms of PF, its pathogenesis remains elusive. This review provides an in-depth exploration of the latest insights into PF pathophysiology, diagnosis, treatment, and future perspectives.
Topics: Humans; Pulmonary Fibrosis; Quality of Life; Lung Diseases, Interstitial; Lung; Fibrosis; Clinical Decision-Making
PubMed: 37716906
DOI: 10.1016/j.molmed.2023.08.010 -
International Journal of Molecular... Nov 2022Pulmonary fibrosis is a chronic progressive lung disease that steadily leads to lung architecture disruption and respiratory failure. The development of pulmonary... (Review)
Review
Pulmonary fibrosis is a chronic progressive lung disease that steadily leads to lung architecture disruption and respiratory failure. The development of pulmonary fibrosis is mostly the result of previous acute lung inflammation, caused by a wide variety of etiological factors, not resolved over time and causing the deposition of fibrotic tissue in the lungs. Despite a long history of study and good coverage of the problem in the scientific literature, the effective therapeutic approaches for pulmonary fibrosis treatment are currently lacking. Thus, the study of the molecular mechanisms underlying the transition from acute lung inflammation to pulmonary fibrosis, and the search for new molecular markers and promising therapeutic targets to prevent pulmonary fibrosis development, remain highly relevant tasks. This review focuses on the etiology, pathogenesis, morphological characteristics and outcomes of acute lung inflammation as a precursor of pulmonary fibrosis; the pathomorphological changes in the lungs during fibrosis development; the known molecular mechanisms and key players of the signaling pathways mediating acute lung inflammation and pulmonary fibrosis, as well as the characteristics of the most common in vivo models of these processes. Moreover, the prognostic markers of acute lung injury severity and pulmonary fibrosis development as well as approved and potential therapeutic approaches suppressing the transition from acute lung inflammation to fibrosis are discussed.
Topics: Humans; Pulmonary Fibrosis; Prognosis; Lung; Pneumonia; Fibrosis; Inflammation
PubMed: 36499287
DOI: 10.3390/ijms232314959 -
Nature Reviews. Disease Primers Oct 2017Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by progressive lung scarring and the histological picture of usual interstitial... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by progressive lung scarring and the histological picture of usual interstitial pneumonia (UIP). It is associated with increasing cough and dyspnoea and impaired quality of life. IPF affects ∼3 million people worldwide, with incidence increasing dramatically with age. The diagnostic approach includes the exclusion of other interstitial lung diseases or overlapping conditions and depends on the identification of the UIP pattern, usually with high-resolution CT; lung biopsy might be required in some patients. The UIP pattern is predominantly bilateral, peripheral and with a basal distribution of reticular changes associated with traction bronchiectasis and clusters of subpleural cystic airspaces. The biological processes underlying IPF are thought to reflect an aberrant reparative response to repetitive alveolar epithelial injury in a genetically susceptible ageing individual, although many questions remain on how to define susceptibility. Substantial progress has been made in the understanding of the clinical management of IPF, with the availability of two pharmacotherapeutic agents, pirfenidone and nintedanib, that decrease physiological progression and likely improve progression-free survival. Current efforts are directed at identifying IPF early, potentially relying on combinations of biomarkers that include circulating factors, demographics and imaging data.
Topics: Humans; Idiopathic Pulmonary Fibrosis
PubMed: 29052582
DOI: 10.1038/nrdp.2017.74 -
Molecular Aspects of Medicine Feb 2019Idiopathic pulmonary fibrosis (IPF) is a progressive and terminal lung disease with no known cure. IPF is a disease of aging, with median age of diagnosis over 65 years.... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a progressive and terminal lung disease with no known cure. IPF is a disease of aging, with median age of diagnosis over 65 years. Median survival is between 3 and 5 years after diagnosis. IPF is characterized primarily by excessive deposition of extracellular matrix (ECM) proteins by activated lung fibroblasts and myofibroblasts, resulting in reduced gas exchange and impaired pulmonary function. Growing evidence supports the concept of a pro-fibrotic environment orchestrated by underlying factors such as genetic predisposition, chronic injury and aging, oxidative stress, and impaired regenerative responses may account for disease development and persistence. Currently, two FDA approved drugs have limited efficacy in the treatment of IPF. Many of the genes and gene networks associated with lung development are induced or activated in IPF. In this review, we analyze current knowledge in the field, gained from both basic and clinical research, to provide new insights into the disease process, and potential approaches to treatment of pulmonary fibrosis.
Topics: Animals; Biomarkers; Cellular Microenvironment; Disease Susceptibility; Homeodomain Proteins; Humans; Myofibroblasts; Pulmonary Fibrosis; Signal Transduction; Stromal Cells; Trans-Activators; Transforming Growth Factor beta
PubMed: 30130563
DOI: 10.1016/j.mam.2018.08.004 -
Methods in Molecular Biology (Clifton,... 2017Interstitial lung disease (ILD) comprises a large number of chronic lung disease characterized by varying degrees of inflammation and fibrosis. Mostly they are...
Interstitial lung disease (ILD) comprises a large number of chronic lung disease characterized by varying degrees of inflammation and fibrosis. Mostly they are idiopathic including idiopathic pulmonary fibrosis (IPF), which is a specific disorder characterized by progressive fibrosis leading commonly to end-stage lung disease, respiratory failure, and fatal outcome. IPF and many of these fibrotic ILDs lack effective therapy despite recent approval of two drugs to slow progression in certain IPF patients. Because there are no natural models for IPF, the use of animal models that reproduce key known features of the disease is warranted. Thus, different animal models have been developed to investigate key mechanisms underlying pathogenesis of pulmonary fibrosis and identify potential therapeutic targets for IPF. While no animal model can recapitulate all features of human disease, several are available to address select features of IPF and other fibrotic ILDs. Historically, among the first to be developed and used widely is the bleomycin model, which is the best-characterized and currently most extensively used animal model due to its ability to reproduce many aspects of IPF and other fibrotic ILDs, good reproducibility, and ease of induction. Studies using the bleomycin model have identified many of the cellular and molecular mechanisms now recognized as being important in pathogenesis of IPF and other fibrotic ILDs, as well as novel therapies for these diseases, including two recent drugs approved for treatment of IPF. This chapter will describe commonly used techniques for induction of the model by endotracheal administration of bleomycin through surgical and nonsurgical (transoral instillation).
Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Disease Models, Animal; Disease Progression; Drug Administration Routes; Female; Genetic Predisposition to Disease; Humans; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Male; Mice; Pulmonary Fibrosis; Rats; Sex Factors
PubMed: 28836192
DOI: 10.1007/978-1-4939-7113-8_2 -
The American Journal of the Medical... May 2019The incidence and prevalence of idiopathic pulmonary fibrosis (IPF) is increasing worldwide. This, combined with its poor prognosis and unpredictable natural history,... (Review)
Review
The incidence and prevalence of idiopathic pulmonary fibrosis (IPF) is increasing worldwide. This, combined with its poor prognosis and unpredictable natural history, has amplified the importance of an accurate diagnosis and monitoring. A diagnosis of exclusion, IPF requires a comprehensive clinical evaluation. This results in a clinical context that provides the backdrop for interpretation of the chest imaging and histopathology. A confident or probable usual interstitial pneumonia chest imaging pattern on high-resolution computerized tomography may be diagnostic in the correct clinical context. Outcomes for IPF are unpredictable, ranging from rapid progression with death within months to prolonged stability. Disease activity is monitored by clinical and physiology measures with a declining forced vital capacity, a recognized measure of progression. The available treatments, pirfenidone and nintedanib, are effective at reducing the expected decline in forced vital capacity.
Topics: Humans; Idiopathic Pulmonary Fibrosis
PubMed: 31010461
DOI: 10.1016/j.amjms.2019.02.013 -
Nature Communications Nov 2022Pulmonary fibrosis is a chronic interstitial lung disease that causes irreversible and progressive lung scarring and respiratory failure. Activation of fibroblasts plays...
Pulmonary fibrosis is a chronic interstitial lung disease that causes irreversible and progressive lung scarring and respiratory failure. Activation of fibroblasts plays a central role in the progression of pulmonary fibrosis. Here we show that platelet endothelial aggregation receptor 1 (PEAR1) in fibroblasts may serve as a target for pulmonary fibrosis therapy. Pear1 deficiency in aged mice spontaneously causes alveolar collagens accumulation. Mesenchyme-specific Pear1 deficiency aggravates bleomycin-induced pulmonary fibrosis, confirming that PEAR1 potentially modulates pulmonary fibrosis progression via regulation of mesenchymal cell function. Moreover, single cell and bulk tissue RNA-seq analysis of pulmonary fibroblast reveals the expansion of Activated-fibroblast cluster and enrichment of marker genes in extracellular matrix development in Pear1 fibrotic lungs. We further show that PEAR1 associates with Protein Phosphatase 1 to suppress fibrotic factors-induced intracellular signalling and fibroblast activation. Intratracheal aerosolization of monoclonal antibodies activating PEAR1 greatly ameliorates pulmonary fibrosis in both WT and Pear1-humanized mice, significantly improving their survival rate.
Topics: Mice; Animals; Pulmonary Fibrosis; Mice, Inbred C57BL; Fibroblasts; Extracellular Matrix; Bleomycin
PubMed: 36402779
DOI: 10.1038/s41467-022-34870-w