Idiopathic pulmonary fibrosis.
Sharma O P
Current opinion in pulmonary medicine
Idiopathic pulmonary fibrosis (IPF), or cryptogenic fibrosing alveolitis as it is known in the United Kingdom and Europe, is perhaps one of the most complex and frustrating pulmonary disorders. The cause of this illness is unknown. Treatment often founders in a mire of discontent, dissatisfaction, and failure. In fact, the philosophic homily "If you do not know where you are going, then any road will take you there" in a curious way sums up the trials and tribulations of treating idiopathic interstitial fibrosis.
10.1097/00063198-199609000-00001
Overview of pulmonary fibrosis.
Green Francis H Y
Chest
Pulmonary fibrosis is a component of over 200 interstitial lung diseases. Some have known etiologies, however, for many diseases, the etiology remains unknown or obscure. This brief review examines the prevalence and classification of these diseases, the approach to be taken for the investigation of a patient suspected of having pulmonary fibrosis, the indications for the performance of lung biopsy, and current thoughts concerning the pathogenesis of the idiopathic forms of fibrotic lung disease. A brief review of established and emerging therapeutic strategies is included.
10.1378/chest.122.6_suppl.334s
Idiopathic pulmonary fibrosis.
du Bois R M
Annual review of medicine
Idiopathic pulmonary fibrosis kills half of its victims within five years of diagnosis. Currently available treatment regimens are disappointing, and the incidence of the disease appears to be increasing. Newer techniques of imaging coupled with laboratory advances in molecular and cellular biology may produce new strategies for modulating the disease process. This article explores new approaches to the diagnosis and management of idiopathic pulmonary fibrosis.
10.1146/annurev.me.44.020193.002301
Antifibrotic therapy in progressive pulmonary fibrosis: a review of recent advances.
Expert review of respiratory medicine
INTRODUCTION:Progressive pulmonary fibrosis (PPF) is a manifestation of a heterogenous group of underlying interstitial lung disease (ILD) diagnoses, defined as non-idiopathic pulmonary fibrosis (IPF) progressive fibrotic ILD meeting at least two of the following criteria in the previous 12 months: worsening respiratory symptoms, absolute decline in forced vital capacity (FVC) more than or equal to 5% and/or absolute decline in diffusing capacity for carbon monoxide (DLCO) more than or equal to 10% and/or radiological progression. AREAS COVERED:The authors subjectively reviewed a synthesis of literature from PubMed to identify recent advances in the diagnosis and characterisation of PPF, treatment recommendations, and management challenges. This review provides a comprehensive summary of recent advances and highlights future directions for the diagnosis, management, and treatment of PPF. EXPERT OPINION:Recent advances in defining the criteria for PPF diagnosis and licensing of treatment are likely to support further characterisation of the PPF patient population and improve our understanding of prevalence. The diagnosis of PPF remains challenging with the need for a specialised ILD multidisciplinary team (MDT) approach. The evidence base supports the use of immunomodulatory therapy to treat inflammatory ILDs and antifibrotic therapy where PPF develops. Treatment needs to be tailored to the specific underlying disease and determined on a case-by-case basis.
10.1080/17476348.2024.2375420
The bleomycin animal model: a useful tool to investigate treatment options for idiopathic pulmonary fibrosis?
Moeller Antje,Ask Kjetil,Warburton David,Gauldie Jack,Kolb Martin
The international journal of biochemistry & cell biology
Different animal models of pulmonary fibrosis have been developed to investigate potential therapies for idiopathic pulmonary fibrosis (IPF). The most common is the bleomycin model in rodents (mouse, rat and hamster). Over the years, numerous agents have been shown to inhibit fibrosis in this model. However, to date none of these compounds are used in the clinical management of IPF and none has shown a comparable antifibrotic effect in humans. We performed a systematic review of publications on drug efficacy studies in the bleomycin model to evaluate the value of this model regarding transferability to clinical use. Between 1980 and 2006 we identified 240 experimental studies describing beneficial antifibrotic compounds in the bleomycin model. 222 of those used a preventive regimen (drug given < or =7 days after last bleomycin application), only 13 were therapeutic trials (>7 days after last bleomycin application). In 5 studies we did not find enough details about the timing of drug application to allow inter-study comparison. It is critical to distinguish between drugs interfering with the inflammatory and early fibrogenic response from those preventing progression of fibrosis, the latter likely much more meaningful for clinical application. All potential antifibrotic compounds should be evaluated in the phase of established fibrosis rather than in the early period of bleomycin-induced inflammation for assessment of its antifibrotic properties. Further care should be taken in extrapolation of drugs successfully tested in the bleomycin model due to partial reversibility of bleomycin-induced fibrosis over time. The use of alternative and more robust animal models, which better reflect human IPF, is warranted.
10.1016/j.biocel.2007.08.011
Pulmonary Fibrosis as a Result of Acute Lung Inflammation: Molecular Mechanisms, Relevant In Vivo Models, Prognostic and Therapeutic Approaches.
International journal of molecular sciences
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.
10.3390/ijms232314959
Pulmonary fibrosis, part I: epidemiology, pathogenesis, and diagnosis.
Meyer Keith C
Expert review of respiratory medicine
INTRODUCTION: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.
10.1080/17476348.2017.1312346
Pulmonary fibrosis: from pathogenesis to clinical decision-making.
Trends in molecular medicine
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.
10.1016/j.molmed.2023.08.010
Mechanisms of pulmonary fibrosis.
Thannickal Victor J,Toews Galen B,White Eric S,Lynch Joseph P,Martinez Fernando J
Annual review of medicine
Tissue injury evokes highly conserved, tightly regulated inflammatory responses and less well-understood host repair responses. Both inflammation and repair involve the recruitment, activation, apoptosis, and eventual clearance of key effector cells. In this review, we propose the concept of pulmonary fibrosis as a dysregulated repair process that is perpetually "turned on" even though classical inflammatory pathways may be dampened or "switched off." Significant regional heterogeneity, with varied histopathological patterns of inflammation and fibrosis, has been observed in individual patients with idiopathic pulmonary fibrosis. We discuss environmental factors and host response factors, such as genetic susceptibility and age, that may influence these varied manifestations. Better understanding of the mechanisms of lung repair, which include alveolar reepithelialization, myofibroblast differentiation/activation, and apoptosis, should offer more effective therapeutic options for progressive pulmonary fibrosis.
10.1146/annurev.med.55.091902.103810