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.


RESULTS
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).


CONCLUSIONS
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.


BACKGROUND
Gilead Sciences.
University of Washington, Seattle, WA, USA. Electronic address: graghu@u.washington.edu.
Ganesh
G
Raghu
University of Colorado, Denver, CO, USA.
David
D
Lynch
University of Washington, Seattle, WA, USA.
J David
JD
Godwin
University of California, San Francisco, CA, USA.
Richard
R
Webb
Mayo Clinic, Scottsdale, AZ, USA.
Thomas V
TV
Colby
Mayo Clinic, Scottsdale, AZ, USA.
Kevin O
KO
Leslie
Klinikum der Ludwig-Maximilians-Universität Munich, Munich, Germany.
Juergen
J
Behr
University of Colorado, Denver, CO, USA.
Kevin K
KK
Brown
Mater Misericordiae Hospital, Dublin, Ireland.
James J
JJ
Egan
University of Michigan, Ann Arbor, MI, USA.
Kevin R
KR
Flaherty
University of Michigan, Ann Arbor, MI, USA.
Fernando J
FJ
Martinez
Royal Brompton Hospital, Chelsea, London, UK.
Athol U
AU
Wells
Gilead Sciences, Seattle, WA, USA.
Lixin
L
Shao
Gilead Sciences, Seattle, WA, USA.
Huafeng
H
Zhou
Gilead Sciences, Seattle, WA, USA.
Patricia S
PS
Pedersen
Perceptive Informatics, Boston, MA, USA.
Rohit
R
Sood
Cardeas Pharma, Seattle, WA, USA.
A Bruce
AB
Montgomery
Gilead Sciences, Seattle, WA, USA.
Thomas G
TG
O'Riordan
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D017326:Clinical Trials, Phase III as Topic; D003937:Diagnosis, Differential; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000000981:diagnostic imaging* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D014057:Tomography, X-Ray Computed / Q000379:methods*