Diagnosis of idiopathic pulmonary fibrosis with high-resolution CT in patients with little or no radiological evidence of honeycombing: secondary analysis of a randomised, controlled trial.

BACKGROUND: Present guidelines for the diagnosis of idiopathic pulmonary fibrosis require histological confirmation of surgical lung biopsy samples when high-resolution CT images are not definitive for usual interstitial pneumonia. We aimed to assess the predictive value of high-resolution CT in a cohort of patients with suspected idiopathic pulmonary fibrosis from a previous randomised trial.

METHODS: ARTEMIS-IPF was a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial of ambrisentan for adults aged 40-80 years with well-defined idiopathic pulmonary fibrosis and 5% or less honeycombing on high-resolution CT. In December, 2010, an interim analysis showed lack of efficacy and the trial was stopped. In the present follow-on analysis, we assessed patients who were screened for ARTEMIS-IPF who underwent high-resolution CT as part of screening and surgical lung biopsy as part of standard clinical care. A radiologist and a pathologist from a central panel independently assessed anonymised CT scans and biopsy samples. We calculated the positive and negative predictive value of high-resolution CT (classified as usual interstitial pneumonia, possible usual interstitial pneumonia, and inconsistent with usual interstitial pneumonia) for confirmation of histological patterns of usual interstitial pneumonia. This study is registered with ClinicalTrials.gov, number NCT00768300.

FINDINGS: 315 (29%) of 1087 consecutively screened patients in ARTEMIS-IPF had both high-resolution CT and surgical lung biopsy samples. 108 of 111 patients who met high-resolution CT criteria for usual interstitial pneumonia had histologically confirmed usual interstitial pneumonia (positive predictive value 97·3%, 95% CI 92·3-99·4), as did 79 of 84 patients who met high-resolution CT criteria for possible usual interstitial pneumonia (94·0%, 86·7-98·0). 22 of 120 patients had an inconsistent high-resolution CT pattern for usual interstitial pneumonia that was histologically confirmed as not or possible usual interstitial pneumonia (negative predictive value 18·3%, 95% CI 11·9-26·4).

INTERPRETATION: In the appropriate clinical setting, for patients with possible usual interstitial pneumonia pattern on high resolution CT, surgical lung biopsy sampling might not be necessary to reach a diagnosis of idiopathic pulmonary fibrosis if high-resolution CT scans are assessed by experts at regional sites familiar with patterns of usual interstitial pneumonia and management of idiopathic interstitial pneumonia.

FUNDING: Gilead Sciences.