Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases

Cottin, Vincent; Hirani, Nikhil; Hotchkin, David; Nambiar, Anoop M.; Ogura, Takashi; Otaola, María; Skowasch, Dirk; Park, Jong Sun; Poonyagariyagorn, Hataya; Wuyts, Wim; Wells, Athol U.

doi:10.1183/16000617.0076-2018

Cited by 468 publications

(423 citation statements)

References 115 publications

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“…A terminology recently used to describe fibrosing ILDs with a progressive phenotype is progressive-fibrosing ILD (PF-ILD) [2]. For details on the diagnosis and clinical course of ILDs with a progressive-fibrosing phenotype, please refer to COTTIN et al [5] in this issue of the European Respiratory Review. Data on the prevalence and incidence of ILDs other than IPF with a progressive-fibrosing phenotype are limited, in part due to the complexity and rarity of diagnosis.…”

Section: Introductionmentioning

confidence: 99%

The epidemiology of idiopathic pulmonary fibrosis and interstitial lung diseases at risk of a progressive-fibrosing phenotype

et al. 2018

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@ERSpublications ILDs with a progressive-fibrosing phenotype appear to be more common in older adults and are associated with a complex network of environmental and genetic factors. Further epidemiological studies are warranted to help identify these patients. http://ow.ly/SY6m30mWytM Cite this article as: Olson AL, Gifford AH, Inase N, et al. The epidemiology of idiopathic pulmonary fibrosis and interstitial lung diseases at risk of a progressive-fibrosing phenotype. Eur Respir Rev 2018; 27: 180077 [https://doi.ABSTRACT The availability of epidemiological data relating to interstitial lung diseases (ILDs) has increased over recent years, but information on the prevalence and incidence of ILDs of different aetiologies remains limited. Despite global distribution, the proportion of patients who develop a progressive phenotype across different ILDs is not well known. Disease behaviour is well documented in idiopathic pulmonary fibrosis but idiosyncratic in other ILDs that may present a progressive fibrosing phenotype. Possible reasons may include the heterogeneous nature of the aetiology, the complexity of diagnosis (and subsequent documentation of cases) and the methods employed to retrospectively analyse patient databases. This review presents a broad overview of the epidemiological data available for ILDs that may present a progressive-fibrosing phenotype, collectively and stratified according to clinical classification. We also note where further data are needed in comparison to the well-studied IPF indication.

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Section: Introductionmentioning

confidence: 99%

The epidemiology of idiopathic pulmonary fibrosis and interstitial lung diseases at risk of a progressive-fibrosing phenotype

et al. 2018

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“…Several studies are underway, where, for example, those with any CTD with a UIP or fibrotic NSIP (‘progressive’) pattern but not OP or cellular NSIP pattern (generally better prognosis without fibrosis) will receive anti‐fibrotic treatment, which so far has only been studied in IPF. The results will potentially significantly change the treatment approach and are keenly awaited …”

Section: Treatment Of Ildmentioning

confidence: 99%

“…The results will potentially significantly change the treatment approach and are keenly awaited. 52,53 Anti-fibrotic therapy Trials of anti-fibrotics arose from basic research in animal models demonstrating the underlying fibrotic pathogenesis including an appreciation of aberrant wound healing and deposition of collagen in the extracellular matrix as key features. Presently, there are only two licensed drugs in the treatment of IPF: pirfenidone and nintedanib.…”

Section: Treatment Of Ildmentioning

confidence: 99%

Idiopathic and immune‐related pulmonary fibrosis: diagnostic and therapeutic challenges

2019

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Interstitial lung disease (ILD) encompasses a large group of pulmonary conditions sharing common clinical, radiological and histopathological features as a consequence of fibrosis of the lung interstitium. The majority of ILDs are idiopathic in nature with possible genetic predisposition, but is also well recognised as a complication of connective tissue disease or with certain environmental, occupational or drug exposures. In recent years, a concerted international effort has been made to standardise the diagnostic criteria in ILD subtypes, formalise multidisciplinary pathways and standardise treatment recommendations. In this review, we discuss some of the current challenges around ILD diagnostics, the role of serological testing, especially, in light of the new classification of Interstitial Pneumonia with Autoimmune Features (IPAF) and discuss the evidence for therapies targeted at idiopathic and immune‐related pulmonary fibrosis.

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“…Pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF), is frequently fatal with existing treatments slowing progression rather than curing the disease (8). The causes and non-genetic risk factors for IPF are poorly understood, with several studies implicating age, sex, smoking and more recently air pollution (9).…”

Section: Introductionmentioning

confidence: 99%

The circadian clock protein REVERBα inhibits pulmonary fibrosis development

Cunningham¹,

Meijer²,

Nazgiewicz³

et al. 2019

Preprint

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Pulmonary inflammatory responses lie under circadian control; however the importance of circadian mechanisms in fibrosis is not understood. Here, we identify a striking change to these mechanisms resulting in a gain of amplitude and lack of synchrony within pulmonary fibrotic tissue. These changes result from an infiltration of mesenchymal cells, an important cell type in the pathogenesis of pulmonary fibrosis. Mutation of the core clock protein REVERBα in these cells exacerbated the development of bleomycin-induced fibrosis, whereas mutation of REVERBα in club or myeloid cells had no effect on the bleomycin phenotype. Knockdown of REVERBα revealed regulation of the poorly described transcription factor TBPL1. Both REVERBα and TBPL1 altered integrinβ1 focal adhesion formation, resulting in increased myofibroblast activation. The translational importance of our findings was established through analysis of two human cohorts. In the UK Biobank circadian strain markers (sleep length, chronotype and shift work) are associated with pulmonary fibrosis making them novel risk factors. In a separate cohort REVERBα expression was increased in human idiopathic pulmonary fibrosis (IPF) lung tissue. Pharmacological targeting of REVERBα inhibited myofibroblast activation in IPF fibroblasts and collagen secretion in organotypic cultures from IPF patients, suggesting targeting REVERBα could be a viable therapeutic approach.SignificanceThe circadian clock plays an essential role in energy metabolism, and inflammation. In contrast the importance of the clock in the pathogenesis of fibrosis remains poorly explored. This study describes a striking alteration in circadian biology during pulmonary fibrosis where the relatively arrhythmic alveolar structures gain circadian but desynchronous rhythmicity due to infiltration by fibroblasts. Disruption of the clock in these cells, which are not widely implicated in circadian pathophysiology, results in a pro-fibrotic phenotype. Translation of these findings in humans revealed previously unrecognised important circadian risk factors for pulmonary fibrosis (sleep length, chronotype and shift work). In addition, targeting REVERBα repressed collagen secretion from human fibrotic lung tissue making this protein a promising therapeutic target.

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Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases

Cited by 468 publications

References 115 publications

The epidemiology of idiopathic pulmonary fibrosis and interstitial lung diseases at risk of a progressive-fibrosing phenotype

The epidemiology of idiopathic pulmonary fibrosis and interstitial lung diseases at risk of a progressive-fibrosing phenotype

Idiopathic and immune‐related pulmonary fibrosis: diagnostic and therapeutic challenges

The circadian clock protein REVERBα inhibits pulmonary fibrosis development

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