Progression in the Management of Non-Idiopathic Pulmonary Fibrosis Interstitial Lung Diseases, Where Are We Now and Where We Would Like to Be

A significant proportion of patients with interstitial lung disease (ILD) may develop a progressive fibrosing phenotype characterized by worsening of symptoms and pulmonary function, progressive fibrosis on chest computed tomography and increased mortality. The clinical course in these patients mimics the relentless progressiveness of idiopathic pulmonary fibrosis (IPF). Common pathophysiological mechanisms such as a shared genetic susceptibility and a common downstream pathway—self-sustaining fibroproliferation—support the concept of a progressive fibrosing phenotype, which is applicable to a broad range of non-IPF ILDs. While antifibrotic drugs became the standard of care in IPF, immunosuppressive agents are still the mainstay of treatment in non-IPF fibrosing ILD (F-ILD). However, recently, randomized placebo-controlled trials have demonstrated the efficacy and safety of antifibrotic treatment in systemic sclerosis-associated F-ILD and a broad range of F-ILDs with a progressive phenotype. This review summarizes the current pharmacological management and highlights the unmet needs in patients with non-IPF ILD.

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Idiopathic pulmonary fibrosis: possibilities of multidisciplinary diagnostic approach

Russian Pulmonology ◽

10.18093/0869-0189-2018-28-5-622-625 ◽

2018 ◽

Vol 28 (5) ◽

pp. 622-625

Author(s):

A. М. Kardangusheva ◽

Н. A. Sabanchieva

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Biopsy ◽

Poor Prognosis ◽

Lung Diseases ◽

Multidisciplinary Approach ◽

Usual Interstitial Pneumonia ◽

Interstitial Lung Diseases ◽

High Resolution Computed Tomography ◽

Antifibrotic Drugs

Idiopathic pulmonary fibrosis (IPF) is the commonest form of idiopathic interstitial pneumonias with very poor prognosis. Currently, diagnostic and treatment approaches to this disease have been revised. Confirmation of the diagnosis requires careful exclusion of other known causes of interstitial lung diseases and the presence of usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRTC) and/or on lung biopsy. Also, multidisciplinary discussion involving experts with experience in the diagnosis of interstitial lung diseases is recommended. Given recent knowledge on pathogenesis of IPF antifibrotic drugs are recommended for the therapy of this disease. A clinical case that demonstrates the multidisciplinary approach to diagnosis of IPF is reported in this article.

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Antifibrotic therapy for fibrotic lung disease beyond idiopathic pulmonary fibrosis

European Respiratory Review ◽

10.1183/16000617.0022-2019 ◽

2019 ◽

Vol 28 (153) ◽

pp. 190022 ◽

Cited By ~ 24

Author(s):

Bridget F. Collins ◽

Ganesh Raghu

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Disease ◽

Lung Diseases ◽

Standard Of Care ◽

Interstitial Lung Diseases ◽

High Resolution Computed Tomography ◽

Pharmacological Agents ◽

Antifibrotic Therapy ◽

Fibrotic Lung Diseases

Two antifibrotic medications (nintedanib and pirfenidone) were recommended (conditionally) for the treatment of patients with idiopathic pulmonary fibrosis (IPF) in the 2015 IPF evidence-based guidelines. These medications have been shown to reduce the rate of decline in forced vital capacity among patients with IPF over time and are the only two disease-modulating pharmacological agents approved by regulatory agencies and available for clinical use worldwide. With the evolved standard of care for interstitial lung disease evaluation including routine use of high-resolution computed tomography, fibrotic lung diseases other than IPF are increasingly recognised. In addition, it is becoming evident that genetic and pathophysiological mechanisms as well as disease behaviour in patients manifesting other “non-IPF progressive fibrotic interstitial lung diseases” (non-IPF-PF) may be similar to those in patients with IPF. Thus, it is biologically plausible that pharmacological agents with antifibrotic properties may be efficacious in non-IPF-PF. Indeed, studies are underway or planned to assess the safety and efficacy of nintedanib or pirfenidone among patients with several non-IPF fibrotic lung diseases. In this review, we briefly summarise the use of pirfenidone and nintedanib in IPF as well as the rationale and potential for use of these medications in non-IPF-PF that are being investigated in ongoing and upcoming clinical trials.

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Antifibrotic Therapies and Progressive Fibrosing Interstitial Lung Disease (PF-ILD): Building on INBUILD

Journal of Clinical Medicine ◽

10.3390/jcm10112285 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2285

Author(s):

John N. Shumar ◽

Abhimanyu Chandel ◽

Christopher S. King

Keyword(s):

Interstitial Lung Disease ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Disease ◽

Lung Diseases ◽

Interstitial Lung Diseases ◽

Treatment Pathway ◽

Antifibrotic Therapy ◽

New Treatment ◽

Fibrotic Lung Diseases

Progressive fibrosing interstitial lung disease (PF-ILD) describes a phenotypic subset of interstitial lung diseases characterized by progressive, intractable lung fibrosis. PF-ILD is separate from, but has radiographic, histopathologic, and clinical similarities to idiopathic pulmonary fibrosis. Two antifibrotic medications, nintedanib and pirfenidone, have been approved for use in patients with idiopathic pulmonary fibrosis. Recently completed randomized controlled trials have demonstrated the clinical efficacy of antifibrotic therapy in patients with PF-ILD. The validation of efficacy of antifibrotic therapy in PF-ILD has changed the treatment landscape for all of the fibrotic lung diseases, providing a new treatment pathway and opening the door for combined antifibrotic and immunosuppressant drug therapy to address both the fibrotic and inflammatory components of ILD characterized by mixed pathophysiologic pathways.

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

European Respiratory Review ◽

10.1183/16000617.0077-2018 ◽

2018 ◽

Vol 27 (150) ◽

pp. 180077 ◽

Cited By ~ 34

Author(s):

Amy L. Olson ◽

Alex H. Gifford ◽

Naohiko Inase ◽

Evans R. Fernández Pérez ◽

Takafumi Suda

Keyword(s):

At Risk ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Diseases ◽

Epidemiological Data ◽

Interstitial Lung Diseases ◽

Global Distribution ◽

Clinical Classification ◽

Heterogeneous Nature ◽

Broad Overview

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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Idiopathic Pulmonary Fibrosis

Chest Imaging ◽

10.1093/med/9780199858064.003.0078 ◽

2019 ◽

pp. 453-457

Author(s):

Cylen Javidan-Nejad

Keyword(s):

Lung Cancer ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Pulmonary Edema ◽

Interstitial Pneumonia ◽

Lung Diseases ◽

Usual Interstitial Pneumonia ◽

Primary Lung Cancer ◽

Interstitial Lung Diseases ◽

Pathologic Diagnosis

Idiopathic pulmonary fibrosis (IPF) represents one of the most common chronic interstitial lung diseases. Usual interstitial pneumonia (UIP) is the pathologic diagnosis of IPF and can be diagnosed when honeycombing is present with a basilar and peripheral predominance and findings not typical of UIP are absent. In the current era, when a diagnosis of UIP is made with confidence on HRCT, biopsy can be avoided. Yet, one must be familiar with mimics of UIP/IPF (most notably pulmonary edema superimposed on emphysema) to avoid confusion misdiagnosis. Radiologists must also be familiar with potential complications of UIP including progression, infection, accelerated fibrosis (which can be lethal) and primary lung cancer (which has an increased incidence in UIP).

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Dynamics in diagnoses and pharmacotherapy before and after diagnosing idiopathic pulmonary fibrosis

ERJ Open Research ◽

10.1183/23120541.00479-2020 ◽

2020 ◽

Vol 6 (4) ◽

pp. 00479-2020

Author(s):

Jesper Rømhild Davidsen ◽

Lars Christian Lund ◽

Christian B. Laursen ◽

Jesper Hallas ◽

Daniel Pilsgaard Henriksen

Keyword(s):

Drug Use ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Diseases ◽

Interstitial Lung Diseases ◽

Opium Alkaloids ◽

Before And After ◽

Oral Corticosteroids ◽

Drug Treatments ◽

Respiratory Drugs

BackgroundIdiopathic pulmonary fibrosis (IPF) is a well-characterised interstitial lung disease. Typically, IPF diagnosis is delayed due to nonspecific symptoms, but can also be delayed due to treatment attempts on false indication or due to treatment targeting common comorbidities. This observational study aimed to assess the dynamics in the medication and diagnosis patterns in the period before and after an IPF diagnosis.MethodsWe identified all Danish patients with IPF between 2002 and 2017. We evaluated new and ongoing drug treatments and incident diagnoses 36 months before and 12 months after an IPF diagnosis by use of Danish nationwide registries. To aid interpretation, 10 random controls were recruited for each case.ResultsA total of 650 IPF patients were identified (median age 73 years (interquartile range 65–78), 70.3% males). Prior to the IPF diagnosis, the most prevalent diagnoses were dyspnoea and non-IPF interstitial lung diseases. For drug use, IPF patients had higher initiation rates for antibiotics, oral corticosteroids and mucolytics. In terms of drug volume, IPF patients used more respiratory drugs, antibiotics, immunosuppressants, corticosteroids, proton pump inhibitors, benzodiazepines and opium alkaloids within the 6 months preceding their IPF diagnosis, compared to the controls. Overall drug use decreased after an IPF diagnosis, mainly due to a reduced glucocorticoid and cardiovascular drug use.ConclusionAmong IPF patients, an increased drug use was observed for diagnoses with symptoms overlapping those of IPF, particularly this was observed during the last 6 months before an IPF diagnosis. This emphasises the need for an increased IPF awareness.

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CA 19-9 serum levels in patients with end-stage idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs): Correlation with functional decline

Chronic Respiratory Disease ◽

10.1177/1479973120958428 ◽

2020 ◽

Vol 17 ◽

pp. 147997312095842

Author(s):

Elisabetta Balestro ◽

Gioele Castelli ◽

Nicol Bernardinello ◽

Elisabetta Cocconcelli ◽

Davide Biondini ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Diseases ◽

Lung Transplant ◽

Functional Decline ◽

Serum Levels ◽

Interstitial Lung Diseases ◽

Disease Course ◽

Rapid Progressors ◽

End Stage

Idiopathic pulmonary fibrosis presents a progressive and heterogeneous functional decline. CA 19-9 has been proposed as biomarker to predict disease course, but its role remains unclear. We assessed CA 19-9 levels and clinical data in end-stage ILD patients (48 IPF and 20 non-IPF ILD) evaluated for lung transplant, to correlate these levels with functional decline. Patients were categorized based on their rate of functional decline as slow (n = 20; ΔFVC%pred ≤ 10%/year) or rapid progressors (n = 28; ΔFVC%pred ≥ 10%/year). Nearly half of the entire patients (n = 32; 47%) had CA 19-9 levels ≥37kU/L. CA 19-9 levels in IPF were not different from non-IPF ILD populations, however, the latter group had a median CA 19-9 level above the normal cut-off value of 37 KU/l (60 [17–247] kU/L). Among IPF patients, CA 19-9 was higher in slow than in rapid progressors with a trend toward significance (33vs17kU/L; p = 0.055). In the whole population, CA19-9 levels were inversely related with ΔFVC/year (r = −0.261; p = 0.03), this correlation remained in IPF patients, particularly in rapid progressors (r = −0.51; p = 0.005), but not in non. Moreover, IPF rapid progressors with normal CA 19-9 levels showed the greater ΔFVC/year compared to those with abnormal CA 19-9 (0.95 vs. 0.65 L/year; p = 0.03). In patients with end-stage ILD, CA 19-9 may represent a marker of disease severity, whereas its level is inversely correlated with functional decline, particularly among IPF rapid progressors.

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