Elsevier

The Lancet

Volume 389, Issue 10082, 13–19 May 2017, Pages 1941-1952
The Lancet

Seminar
Idiopathic pulmonary fibrosis

https://doi.org/10.1016/S0140-6736(17)30866-8Get rights and content

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.

Section snippets

Epidemiology

Idiopathic pulmonary fibrosis is the most common type of idiopathic interstitial pneumonia. Although the disease has been considered rare, it occurs with similar frequency to that of stomach, brain, and testicular cancers.1, 2 Incidence of idiopathic pulmonary fibrosis has risen over time, and in Europe and North America is estimated to range between 2·8 and 18 cases per 100 000 people per year.2, 3 Little data are available for worldwide variation, but incidence might be lower in Asia and

Pathophysiology

Historically, idiopathic pulmonary fibrosis was considered a chronic inflammatory disorder, which gradually progressed to established fibrosis. However, at the turn of the century, following the recognition that anti-inflammatory therapy did not improve outcome, this concept was reassessed and, subsequently, an immunosuppressive therapeutic strategy incorporating prednisolone and azathioprine was shown to increase mortality.8, 9 Idiopathic pulmonary fibrosis is now generally regarded as a

Clinical presentations, signs, and symptoms

Patients typically present with non-specific symptoms of exertional dyspnoea with or without dry cough (figure 2). This presentation might initially be attributed to ageing, deconditioning, or other comorbidities (eg, smoking history, emphysema, cardiovascular disease, or obesity); therefore, clinical suspicion of idiopathic pulmonary fibrosis by primary care physicians is required to prevent diagnostic delays. Occasionally, patients will present acutely, with days to weeks of respiratory

Diagnosis

Idiopathic pulmonary fibrosis is diagnosed by identification of a pattern of usual interstitial pneumonia on the basis of radiological or histological criteria in patients without evidence of an alternative cause.4, 57, 58 This approach is endorsed in consensus guidelines worldwide and has helped to standardise idiopathic pulmonary fibrosis diagnosis. A major challenge to clinicians is exclusion of other idiopathic interstitial pneumonias and of known causes of interstitial lung disease, such

Clinical management

Prompt referral of patients with known or suspected idiopathic pulmonary fibrosis to a centre with expertise in idiopathic pulmonary fibrosis care is advised, because delayed access is independently associated with increased risk of death.75 Referral provides patients with access to expertise in diagnosis and management, including initiation of disease-modifying therapy, monitoring, side-effect control, and non-pharmacological support (figure 4).4, 76 In addition to idiopathic pulmonary

Disease-modifying therapy

Standardisation of idiopathic pulmonary fibrosis diagnostic criteria has enabled large, multicentre, randomised placebo-controlled trials of proposed disease-modifying drugs. Randomised controlled trials identified that various putative therapies (eg, prednisolone and azathioprine, acetylcysteine, and warfarin) were ineffective or harmful; a landmark contribution to idiopathic pulmonary fibrosis patient care (panel).9, 83 Through these randomised controlled trials, two large phase 3 development

Diagnosis of idiopathic pulmonary fibrosis

Approval of disease-modifying therapies for idiopathic pulmonary fibrosis has increased the focus on early and accurate diagnosis with the aim of improving long-term treatment outcome. The diagnostic certainty of idiopathic pulmonary fibrosis depends on the presence or absence of specific morphological criteria; the approval of safe and effective therapies provides a timely opportunity to review this approach because only patients with idiopathic pulmonary fibrosis can receive these therapies.4

Conclusions and future directions

In less than 10 years, the landscape of idiopathic pulmonary fibrosis has been transformed. Many no longer consider pulmonary fibrosis to be idiopathic, with interaction between causal factors, including genetic polymorphisms, ageing, and environmental exposures, which culminate in a maladaptive repair process of injured lung. Advances in understanding of disease pathogenesis integrated with the establishment of methodologies to do large multicentre randomised controlled trials have resulted in

Search strategy and selection criteria

We searched PubMed for reports published in English between Jan 1, 1996, and Oct 1, 2016, using the search terms “pulmonary fibrosis”, “fibrosing alveolitis”, “usual interstitial pneumonia”, and “nonspecific interstitial pneumonia”. We mostly selected publications from the past 5 years, although we also included highly regarded older publications. Reviews are cited to provide the reader with additional detail and references.

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