Managing diagnostic procedures in idiopathic pulmonary fibrosis

Revised guidelines

The 2000 diagnostic and management guidelines for IPF were updated in 2011 by an international collaboration of the ATS and ERS, as well as the Japanese Respiratory Society (JRS) and the Latin American Thoracic Association (ALAT) [11]. The main objective was to provide simplified and evidence-based criteria that facilitate a more confident clinical diagnosis of IPF. The recommendations were developed from a thorough review of existing published evidence, with the use of expert opinion only when the evidence base was inadequate.

The original 2000 diagnostic criteria proposed that, in an appropriate clinical context, an UIP pattern according to HRCT criteria is sufficient to diagnose IPF without performing a SLB [1, 10]. This proposition was ratified by the revised ATS/ERS/JRS/ALAT 2011 guidelines that established HRCT as having a primary role in the IPF diagnostic pathway. The revised guidelines specifically identify the HRCT features of IPF “UIP”, “possible UIP” and “inconsistent with UIP” patterns (table 3) [11]. The summary of the revised diagnostic criteria is as follows: 1) exclusion of other known causes of ILD (e.g. domestic and occupational environmental exposures, connective tissue disease and drug toxicity); 2) presence of a UIP pattern on HRCT scans in individuals not subjected to SLB; and 3) specific combinations of HRCT and SLB pattern in individuals subjected to SLB.

The HRCT imaging features of UIP are characterised by reticular opacities, often associated with traction bronchiectasis, honeycombing manifested as mainly subpleural cluster cystic airspaces, typically of comparable diameters (3–10 mm, but occasionally larger), with well-defined thickened walls, and the absence of additional radiological features considered incompatible with a diagnosis of IPF [9, 11]. Ground-glass opacities are common, but less extensive than the reticulation, with a characteristically basal and peripheral distribution, though often patchy [2, 3].

The presence or absence of honeycombing

The principle of integrating HRCT with histopathological data in assigning a diagnostic likelihood of IPF is a significant improvement of the 2011 recommendations. Indeed, the strengths and potential drawbacks of the revised IPF guidelines centre largely upon the application and analysis of HRCT. However, one of the most prevalent problems in clinical practice is the classification of patients with a predominantly basal and subpleural distribution of reticular abnormalities typical of IPF, but without honeycombing on HRCT. Atypical HRCT findings include ground-glass opacity, pleural effusion and thickening with nodules and/or scattered cysts. Unfortunately, there is no category in the 2011 guidelines for this constellation of features that are not uncommonly seen in patients with possible IPF in clinical practice, including those with traction bronchiectasis, co-existing emphysema and fibrosis [12], and/or those of ≥60 years of age [9].

The accuracy of a trained observer in discriminating between ILDs and the identification of IPF is approximately 80–90% [13–15]. However, interobserver variation in the distinction between typical and atypical HRCT appearances of IPF is substantial among less experienced observers [16]. Expert interpretation of HRCT data and the identification of honeycombing are therefore central to the diagnosis of IPF [17]. Unfortunately, however, the current HRCT diagnostic recommendations are not implemented uniformly by the majority of radiologists. Thus, additional diagnostic evaluation is often required in patients with possible IPF that have evidence of peripheral basal reticular change in the absence of honeycombing with other atypical HRCT findings.

Surgical lung biopsy

As suggested above, a diagnosis of definite IPF is not usually possible from HRCT appearances alone in at least one-third of cases [3, 18]. As suggested in the 2000 guidelines, the revised 2011 guidelines appropriately recommend that a SLB should be performed when patients present with nondiagnostic scans or if the diagnosis of definite IPF is uncertain [2, 11]. However, a large proportion of patients with suspected IPF cannot undergo a SLB procedure, either because of contraindications (e.g. comorbid conditions, disease severity, advanced age, etc.) or because the patient declines the procedure [19]. Such patients are therefore disenfranchised by the diagnostic criteria and consequently ineligible from receiving novel therapies licensed for use in definite IPF. A clearer separation between patients who can undergo a SLB with an acceptably low risk and those in whom SLB should be avoided would be helpful to clinicians.

Bronchoalveolar lavage

The value of BAL in the diagnosis of IPF is also contentious. The most important application of BAL is to increase the index of suspicion for alternative disorders in patients with suspected IPF, including hypersensitivity pneumonitis and NSIP, by the demonstration of a lymphocytosis (>30%) [20]. The ATS/ERS/JRS/ALAT 2011 guidelines make a weak negative recommendation that BAL cellular analysis should not be performed in the diagnostic evaluation of IPF in the majority of patients, but may be appropriate in a minority of patients [11].

This recommendation is confusing as it may be applied to either of two very dissimilar clinical scenarios. First, if HRCT features are classical for IPF and the clinical context is correct, the patient has definite IPF. Secondly, if the HRCT features are not classical for IPF but IPF is suspected, the diagnostic overlap includes IPF/NSIP, IPF/hypersensitivity penumonitis, IPF/sarcoidosis and IPF/unclassifiable. The combination of such scenarios in a single recommendation is clinically impractical and two independent statements would be preferable. In the British Thoracic Society guidelines on the diagnosis and management of interstitial lung disease, for example, the diagnostic use of BAL is reserved for patients in whom the diagnosis of IPF is uncertain after clinical assessment and HRCT scanning, with the case-by-case exclusion of patients with severe disease, or because a biopsy will ultimately be performed [21].

Rational multidisciplinary clinical approach

The ATS/ERS/JRS/ALAT 2011 guideline recommendations have assisted clinicians in making an evidence-based diagnosis of IPF (fig. 2) [11]. However, no attempt is made to define minimum standards required for the process of a multidisciplinary evaluation of IPF, particularly with respect to HRCT misdiagnosis. A multidisciplinary, dynamic approach within an expert centre and regular collaborative input of clinicians, radiologists, and histopathologists has been shown to improve diagnostic accuracy [22–24]. For example, and where relevant, consultation with the surgeon, pathologist and radiologist in interpreting BAL results, and to determine the exact location(s) of surgical biopsy based on HRCT appearances is advantageous [11]. A nurse specialist should also attend this meeting to oversee and integrate the process.

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Figure 2.

2011 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association diagnostic algorithm for idiopathic pulmonary fibrosis (IPF). ILD: interstitial lung disease; HRCT: high-resolution computed tomography; UIP: usual interstitial pneumonia; MDD: multidisciplinary discussion. Reproduced and modified from [11] with permission from the publisher.