It’s been a few weeks since our most recent ILD roundup – we’re glad to be back! This weeks ILD conference was chock full of pearls as usual.
1. First, we discussed the implications of leukocyte telomere length (LTL) testing on decision to use immunomodulatory therapy. Recall that PANTHER-IPF showed evidence of harm in patients with IPF receiving prednisone, azathioprine and n-acetylcysteine (NAC).
Could LTL serve as a biomarker to predict patients at risk of harm from use of immunomodulatory therapy in IPF?
This question was asked in a recent post-hoc analysis1 of the PANTHER-IPF2 and unpublished ACE-IPF study. The authors found that short LTL (<10%ile) was associated with an increased risk of the composite outcome of death, lung transplantation or FVC decline in those exposed to prednisone/azathioprine/NAC (HR 2.84; 1.02-7.87, p=0.04). This association was not found in either cohort when patients with LTL >10%ile were examined.
The authors propose that this may be related to unmasking of an immune dysfunction phenotype in patients with short LTL through immunosuppression. When the same criteria were applied to an unrelated cohort of patients participating in a longitudinal observational study at UTSW, there was actually a significant improvement in the prednisone/azathioprine/mycophenolate group with LTL >10%ile.
Kaplan-Meier curve – UTSW cohort
2. Our next patient was a woman in her 70s with GERD and chronic joint pain. with CT imaging after mechanical fall concerning for ILD. Has developed progressive DOE over past year, with steroid responsiveness. The overall CT pattern was most consistent with fibrotic NSIP, but perilobular opacities were also noted. A differential consideration of organizing pneumonia3 was discussed.
What is a perilobular opacity?
A perilobular opacity refers to polygonal opacity around interlobular septa and with sparing of the secondary pulmonary lobule. As Dr. Agrawal brought up to the group, this tends to have more diffuse distribution than a a “reversed halo/atoll sign” which is a focal finding.
“Reverse halo”, or “Atoll” sign in organizing pneumonia
Perilobular opacity in association with bronchial wall thickening and bronchial dilation in organizing pneumonia
What are the radiographic features most consistent with organizing pneumonia, and what are their primary differential considerations?
3. A final case we discussed was a former tobacco user in his 70s, with RA on MTX, Humira and prednisone, former asbestos exposure, who presented to VA clinic with progressive DOE over past 6-12 mo. A transbronchial biopsy performed in 2021 with negative cytology for malignancy but otherwise non-diagnostic. CT with showed significant asbestos related pleural disease. Reticulation was seen mostly in association with pleural plaques. Despite the diagnosis of seropositive RA, our multi-disciplinary consensus was asbestos-related pulmonary fibrosis. The question of anti-fibrotic treatment was raised.
What is the evidence for antifibrotic therapy in asbestos-related pulmonary fibrosis?
Remember, the INBUILD4 trial showed evidence of benefit (lower annual rate of FVC decline) for antifibrotics in non-IPF fibrosing ILDs. Did they include asbestos-related fibrosis? Hard to say! Looking at the supplementary information (see Table below), 81/663 patients fell into category of “other ILDs” which did include exposure-related ILDs among others, but didn’t specifically mention asbestosis.
The RELIEF5 study was a phase II placebo controlled RCT that looked at use of antifibrotic agents for non-IPF ILDs (fibrosing NSIP, CHP, and asbestos related pulmonary fibrosis). Patients enrolled had experienced disease progression despite conventional therapy. Of note, only 5 of 127 patients included with asbestos-related pulmonary fibrosis. They followed patients for 48 weeks and reported a significantly lower rate of decline in FVC as a % of predicted value.
The annual rate of decline in FVC (-36.6 vs –114.4, p=0.21) did not meet statistical significance. Why is this relevant? A quick refresher6 on the endpoints for the IPF anti-fibrotic trials:
Sources:
- Am J Respir Crit Care Med. 2019;200(3):336-347. doi:10.1164/rccm.201809-1646OC
- N Engl J Med. 2012;366(21):1968-1977. doi:10.1056/NEJMoa1113354
- Br J Radiol. 2017;90(1071):20160723. doi:10.1259/bjr.20160723
- N Engl J Med. 2019;381(18):1718-1727. doi:10.1056/NEJMoa1908681
- Lancet Respir Med. 2021;9(5):476-486. doi:10.1016/S2213-2600(20)30554-3
- Eur Respir Rev Off J Eur Respir Soc. 2019;28(153):190022. doi:10.1183/16000617.0022-2019