The Clinical Course of Interstitial Pneumonia With Autoimmune Features: an Observational, Prospective Cohort Study

Objective of the study The objective of this study is to investigate the clinical course of IPAF to clarify the prognosis of this condition and to clarify the proportion of patients who develop clear clinical features of CTD over time. Patients will be followed prospectively for a period of 3 years, or until death or lung transplant (LTx). Predictors of LTx-free survival will be studied as well.

Rationale Interstitial pneumonia with autoimmune features (IPAF) is a chronic interstitial lung disease (ILD) with some laboratoristic and/or clinical features of autoimmune disease, but without meeting criteria of connective tissue disease (CTD), and with no other causes of ILD.

It is not uncommon for the interstitial pneumonia to be the first, and possibly the sole, manifestation of an otherwise occult CTD. The current international guidelines for the diagnosis of IIP recommend excluding CTD. For this reason, many cases of ILD with autoimmune features, but not fully meeting criteria for CTD, have been identified. Patients with IPAF, with the current diagnostic criteria, actually represent a sizable proportion of patients with ILD. However, the clinical course, prognosis and treatment approach to these patients remain unclear.

Despite recent efforts to standardize the diagnosis of IPAF, subjects with IPAF represent a very heterogenous group of patients, whose prognosis and clinical course are far from being clear. While the average age of diagnosis is higher than in CTD, there is still a female predominance. An autoimmune "flavor" may not necessarily mean a real autoimmune etiology, but currently the distinction is challenging. From this perspective, a multi-disciplinary approach together with Rheumatologist is particularly important. It also remains to be clarified what proportion of IPAF patients develop clear features of CTD over time. One issue for example is represented by the fact patient with IPAF may be treated with immunosuppressive agents, which may permanently mask the development of systemic features of CTD.

A clear distinction between IPAF and idiopathic pulmonary fibrosis (IPF), one of the most common types of ILD, is at the same time challenging and essential, as treatment is radically different in the two conditions. CTD and IPAF patients can definitely present with the same morphologic (radiographic or pathologic) pattern of usual interstitial pneumonia. However, patients with IPF respond to anti-fibrotic treatment, which is expensive, while patients with ILD secondary to CTD respond to immunosuppressive treatment. From a prognostic point of view, the survival of IPF is considered one of the worst among all types of ILD.