IPAF: Heterogeneity Hurts Clinical Utility

Aaron B. Holley, MD


April 15, 2019

Despite an official research statement[1] on interstitial pneumonia with autoimmune features (IPAF) in 2015, attempts to bring order to the disorganized world of interstitial lung disease (ILD) continue. Pulmonologists often encounter patients with ILD and collagen vascular disease (CVD) who don't meet the rheumatologic criteria for CVD. But, because guidelines and reviews[2,3] recommend that patients with ILD undergo serologic testing for CVD, we "shotgun" a panel of autoantibodies and see what we get. If any of the results are positive, the patients are referred to rheumatology so they can be told they do not have CVD. No one really knows what should happen next.

In a just-published pro-con debate[4,5] on the usefulness of the IPAF classification, both parties acknowledge that the classification scheme from 2015 is a work in progress. The pro authors, one of whom is the first author on that research statement, argue that standardization is a necessary first step to achieve clarity. The con authors feel that too many different pathologies and prognoses can be classified as IPAF, so the designation has no clinical value. They think we need to convince the rheumatologists to include ILD as a diagnostic criterion for CVD (which makes sense, but the pulmonary community alone can't make that happen).

Personally, I think they're both right. As it stands today, "diagnosing" your patient with IPAF might make you feel better, but it won't guide treatment or predict outcomes. You need specifics on the patterns of ILD, the domains that are positive, and the rate of disease progression. IPAF is just too heterogeneous, as evidenced by the variable disease progression seen in existing series.[6] In some, the prognosis is excellent; in others, it is awful.[7] You may let it push you toward using an immunosuppressive instead of an antifibrotic, but if the ILD is usual interstitial pneumonia, it is not clear you should. In fact, the con authors[5] do a good job of describing the wide spectrum of patients who could fall under the IPAF umbrella.

However, let's not judge that research statement on IPAF in a vacuum. Although idiopathic pulmonary fibrosis is relatively well described,[2] the ILD waters are otherwise murky. Take nonspecific interstitial pneumonia (NSIP) as an example. As of 2013, it is officially accepted as a distinct clinically entity,[8] but a 2008 report on idiopathic NSIP is hardly a beacon of clarity.[9] Much of the criticism about IPAF could easily be applied to NSIP—it's heterogeneous and hard to nail down. Confirming a diagnosis of NSIP doesn't mean you know how the patient will respond to immunosuppressive agents or antifibrotics.

So, although IPAF is an important concept, the research statement represents only the beginning of the discussion. And now that we've started it, maybe we can get to work on a proper revision.

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