Idiopathic pulmonary fibrosis Richeldi, Luca, Prof; Collard, Harold R, MD; Jones, Mark G, PhD
The Lancet,
05/2017, Letnik:
389, Številka:
10082
Journal Article
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Summary 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.
CT is increasingly being used to stage and quantify the extent of diffuse lung diseases both in clinical practice and in treatment trials. The role of CT in the assessment of patients entering ...treatment trials has greatly expanded as clinical researchers and pharmaceutical companies have focused their efforts on developing safe and effective drugs for interstitial lung diseases, particularly for idiopathic pulmonary fibrosis. These efforts have culminated in the simultaneous approval by the US Food and Drug Administration of two new drugs for the treatment of idiopathic pulmonary fibrosis. CT features are a key part of the inclusion criteria in many drug trials and CT is now being used to refine the type of patients enrolled. Interest in the potential use of serial CT as an effectiveness endpoint is increasing. For chronic progressive diseases, mortality may not be a feasible endpoint and many surrogate markers have been explored, ranging from pulmonary function decline to biomarkers. However, these surrogate markers are not entirely reliable and combinations of endpoints, including change in disease extent on CT, are being investigated. Methods to assess disease severity with CT range from simple visual estimates to sophisticated quantification by use of software. In this Position Paper, which cannot be regarded as a comprehensive set of guidelines in view of present knowledge, we examine the uses of serial CT in clinical practice and in drug trials and draw attention to uncertainties and challenges for future research.
With the recent development of two effective treatments for patients with idiopathic pulmonary fibrosis, an accurate diagnosis is crucial. The traditional approach to diagnosis emphasises the ...importance of thorough clinical and laboratory evaluations to exclude secondary causes of disease. High-resolution CT is a critical initial diagnostic test and acts as a tool to identify patients who should undergo surgical lung biopsy to secure a definitive histological diagnosis of usual interstitial pneumonia pattern. This diagnostic approach faces several challenges. Many patients with suspected idiopathic pulmonary fibrosis present with atypical high-resolution CT characteristics but are unfit for surgical lung biopsy, therefore preventing a confident diagnosis. The state of the art suggests an iterative, multidisciplinary process that incorporates available clinical, laboratory, imaging, and histological features. Recent research has explored genomic techniques to molecularly phenotype patients with interstitial lung disease. In the future, clinicians will probably use blood-specific or lung-specific molecular markers in combination with other clinical, physiological, and imaging features to enhance diagnostic efforts, refine prognostic recommendations, and influence the initial or subsequent treatment options. There is an urgent and increasing need for well designed, large, prospective studies measuring the effect of different diagnostic approaches. Ultimately, this will help to inform the development of guidelines and tailor clinical practice for the benefit of patients.
Findings from recently published placebo-controlled trials in idiopathic pulmonary fibrosis have established that pirfenidone and nintedanib prevent about 50% of the decline in forced vital capacity ...typically seen in this disease; future trials are therefore unlikely to use placebo as a control group for ethical reasons. Future clinical assessment will probably include add-on trials in which a new drug is combined with an intervention with established efficacy; this development is in turn likely to herald the use of combination regimens in clinical practice. Personalised medicine (the selection of monotherapies on the basis of individualised biomarker signal) is an intrinsically attractive alternative approach, but is unlikely to be useful in routine management of idiopathic pulmonary fibrosis in the medium-term future because of the complex nature of the disease's pathogenesis. In this Personal View, we review the pleiotropic nature of disease pathogenesis in idiopathic pulmonary disease, the use of combination regimens in other selected chronic lung diseases, and the conceptual basis for combination therapies in interstitial lung disorders other than idiopathic pulmonary fibrosis. On the basis of these considerations, and the emergence of data from add-on trials, we believe that the future of management for idiopathic pulmonary fibrosis lies in the development of combination regimens.
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