Review
Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper

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Summary

This Review provides an updated approach to the diagnosis of idiopathic pulmonary fibrosis (IPF), based on a systematic search of the medical literature and the expert opinion of members of the Fleischner Society. A checklist is provided for the clinical evaluation of patients with suspected usual interstitial pneumonia (UIP). The role of CT is expanded to permit diagnosis of IPF without surgical lung biopsy in select cases when CT shows a probable UIP pattern. Additional investigations, including surgical lung biopsy, should be considered in patients with either clinical or CT findings that are indeterminate for IPF. A multidisciplinary approach is particularly important when deciding to perform additional diagnostic assessments, integrating biopsy results with clinical and CT features, and establishing a working diagnosis of IPF if lung tissue is not available. A working diagnosis of IPF should be reviewed at regular intervals since the diagnosis might change. Criteria are presented to establish confident and working diagnoses of IPF.

Introduction

The approval of medical treatments for idiopathic pulmonary fibrosis (IPF) marks a new era in approaching this deadly disease: offering hope to patients and their physicians, a clearer path forward for companies interested in the development of new treatments, and the potential for new biological insights. This new era also offers clinicians the opportunity to review approaches to diagnosis. The diagnostic criteria for IPF published by the American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Latin American Thoracic Association (ALAT) in 20111 have been crucial for defining entry criteria and ensuring appropriate recruitment for prospective clinical trials.2, 3, 4, 5, 6, 7 In turn, these trials, with large cohorts of well characterised patients, have provided considerable new clinically relevant information about disease presentation and its longitudinal behaviour.8, 9 The specific inclusion and exclusion criteria used in these studies have also highlighted the limitations of current diagnostic guidelines, and indicated opportunities for improvement.9, 10

The diagnosis of IPF requires the collaboration of multiple specialists, the ability to interpret and communicate complex clinical data patterns, and to integrate uncertain or sometimes conflicting information. The clinician interprets the history and physical examination of the patient to develop a clinical context, the thoracic radiologist interprets the pattern present on high-resolution CT images of the chest and, if needed, the pathologist interprets the histopathological pattern seen on lung biopsy samples. All the information gained must then be shared in a common language to enable clinical decision making. Since so-called classic clinical stories and patterns are uncommon, some degree of clinical uncertainty is often present, and acknowledgment of this limitation and a clear plan to address it are essential.

For this Review, we identified specific questions pertaining to the diagnosis of IPF (panel 1), and did a search of the medical literature to identify evidence related to the topics identified and that had been published after the 2011 ATS/ERS/JRS/ALAT guidelines.1 Using this research and the expert opinion of members of the Fleischner Society, we provide IPF diagnostic criteria that we believe will be useful for clinicians, clinical trialists, trial sponsors, and other interested groups.

Section snippets

Systematic review

An international multidisciplinary committee, including 17 members of the Fleischner Society with expertise in interstitial lung disease (ILD) and evidence-based medicine (eight pulmonologists, six radiologists, and three pathologists), and a medical librarian expert (SLK), developed the key questions believed to be important for the diagnosis of IPF (panel 1). Several face-to-face meetings were held, in addition to monthly conference calls. We did a literature search with the assistance of a

What specific clinical information is required to exclude other forms of ILD?

A diagnosis of IPF requires exclusion of alternative causes of fibrosing ILD, broadly grouped into systemic and exposure-related disorders. The clinical assessment requires an inquiring mind, a clear understanding of the differential diagnosis for IPF, and a comprehensive and structured approach to help exclude known causes and associations of fibrosing lung disease. A clear focus of a patient's clinical examination should be to establish the clinical probability of IPF, which is particularly

Imaging

CT plays a central role in the assessment of patients with ILD, and can be diagnostic in many situations. When IPF is considered in the differential diagnosis, the radiologist must indicate whether a UIP pattern is present and, if so, what their level of confidence is. Because of its importance, a systematic approach to CT of the chest in patients with suspected UIP is needed. This approach entails evaluation of image quality, precise assessment of specific disease features by use of standard

When is surgical or other biopsy indicated in the diagnosis of IPF?

The presence of a typical or probable UIP pattern on CT provides a diagnosis of IPF in the appropriate clinical context; no additional information is necessary, as discussed in the previous section. A surgical lung biopsy should be considered when the CT pattern is indeterminate or inconsistent with UIP, or when the clinical features suggest an alternative diagnosis (eg, exposures suggestive of hypersensitivity pneumonitis).

The current IPF guidelines1 do not adequately address the diagnostic

Guidance for multidisciplinary diagnosis

Multidisciplinary assessment of a patient with fibrotic ILD is important to establish the diagnosis and level of diagnostic confidence, determine the need for biopsy and other investigations, and help guide management. In the 2011 guidelines1 for the diagnosis and management of IPF, a multidisciplinary diagnosis consisted of the integration of views from radiologists, pathologists, and pulmonary specialists, primarily on the basis of a formulaic tabulated approach. However, the process of

Areas of uncertainty

The understanding of the diagnosis of IPF has many important gaps, and diagnostic guidelines will require regular revision. In this regard, several groups are working on combining imaging and clinical features to refine the assessment of the probability of IPF.11, 132 The clinical significance of atypical features on CT (eg, mosaic attenuation, apical pleuroparenchymal thickening) or by biopsy (eg, granulomas, PPFE) requires further clarification. More work is needed to understand the

Conclusions and recommendations

The clinical, imaging, and histological criteria for diagnosis of IPF continue to evolve. Panel 3 provides some diagnostic parameters that can be followed for patients with suspected IPF based on the clinical diagnostic confidence and radiological and pathological categories discussed in this Review. A diagnosis of IPF can be confidently made in a patient with a typical clinical context of IPF, with a CT pattern of typical or probable UIP. In all other circumstances, multidisciplinary diagnosis

Search strategy and selection criteria

Because the 2011 American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association statement1 was based on a systematic literature search that ended in May, 2010, for this Review we searched for publications from May 1, 2010, through to April 28, 2016, on the Ovid platform in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Abstracts and Reviews of Effects, and Cochrane Database of Systematic

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