ILD Roundup (7/8/22)
1. Interstitial pneumonia with autoimmune features (IPAF) was favored as a differential consideration in a patient who presented to NMH for a third opinion for her ILD
ERS/ATS research statement (Eur Respiratory Journal 2015;46:976-987)
On the spectrum between idiopathic interstitial pneumonias (IIP) and connective-tissue disease associated ILDs (CT-ILD) are patients with IPAF. Oftentimes patients with an “autoimmune flavor” of ILD do not meet criteria for CTD diagnosis.
Why does the distinction matter?
- Identifying underlying etiology impacts treatment and prognosis
- Expedites linkage to rheumatology care, potentially facilitating CTD diagnosis
- Accurate disease epidemiology depends on it
- May aid in elucidation of pathophysiologic mechanism of disease
- Defined criteria facilitate clinical trial design for future research
What are the consensus criteria?
All of the following must be fulfilled:
- Presence of interstitial pneumonia (HRCT/SLB)
- Exclusion of alternative etiologies
- Does not meet criteria for defined connective tissue disease
- At least one feature from 2/3 domains:
- Clinical
- Serologic
- Morphologic
Pearl from case discussion: If histopathology pattern does not fit expectation but another criterion in this domain is met (histopathology predominantly UIP pattern, however, there was presence of lymphoid aggregates), the diagnostic criteria for IPAF may still be satisfied!
2. In the same patient as above, we discussed and ultimately decided against use of azathioprine, because she had some HRCT features suggestive of a UIP pattern
We know that nintedanib (INPULSIS – 2014) and pirfenidone (ASCEND – 2014) are associated with decreased rate of FVC decline in patients with IPF, hence the rationale for their use. Before the advent of antifibrotics, immunosuppressive agents had been used in patients with IPF. Several retrospective studies and small RCTs suggested mortality benefit with combination of steroid + AZA or cyclophosphamide though they were confounded by inclusion of patients who did not meet diagnostic criteria for IPF. Guidelines thus differed: the British Thoracic Society weakly recommended N-acetylcysteine (NAC), prednisolone, and azathioprine based on results from IFIGENIA (decreased decline in FVC and DLCO); whereas, the ATS/ERS recommended lung transplantation and participation in clinical trials. The IFIGENIA trial was limited by substantial drop-out and lack of “no treatment” arm.
Why do we now avoid the use of immunosuppressive medications – and azathioprine in particular – in suspected IPF?
PANTHER-IPF (NEJM 2012;366:1968-1977)
- A double blind RCT wherein a commonly used cocktail of prednisone/azathioprine/NAC was used in 1:1:1 fashion with placebo and NAC alone
- A previous study had shown that triple therapy performed superiorly with regards to VC and DLco preservation compared with prednisone/azathioprine alone, but no placebo-controlled data existed
- Stopped at interim analysis when control group was found to have significant increase in death and hospitalization rates compared to placebo
3. In another patient, the presenter mentioned that hypersensitivity pneumonitis had not been considered in a patient because he did not have any “clear exposure history”.
How often is a diagnosis of HP arrived upon without a clear exposure history? Does identification of an exposure matter in patients with HP?
CHEST 2013;144(5):1644-1651
- In a retrospective review of a longitudinal ILD database, 134 consecutive patients with clinico-radiologic diagnosis of HP found that inciting antigen was not identified in 53% of cases.
- Inability to identify target antigen was associated with significantly shorter survival (HR 1.76; 1.01-3.07) in this same cohort.