I. A 62 yo female with family history of pulmonary fibrosis with an NSIP pattern
What is the relationship between telomere length and familial pulmonary fibrosis?
-Heterozygous mutations in coding regions of two telomerase genes (TERT :: protein component, TERC :: RNA component) have been associated (found in 15% of kindreds) with familial IPF
Pulmonary fibrosis is seen in 50% of women and 60% of men 60 years and older with TERT mutations
-UIP radiograph pattern (74% HRCT) and UIP pathologic pattern (86% surgical lung biopsy) is most commonly encountered
-Even in sporadic cases of IPF, a significantly higher proportion of individuals have telomere lengths <10th percentile compared with controls, even absent TERT/TERC mutations (present in 1-3% of sporadic cases)
Plotting mean telomere length against age with 10-90th percentile in normal controls mapped in blue region
https://www.atsjournals.org/doi/pdf/10.1164/rccm.200804-550OC
https://doi.org/10.1371/journal.pone.0010680
II. 69 yo F with seropositive RA and progressive fibrosing ILD, found to have upper zone predominant fibrosis, honeycombing, TBE.
What HRCT & histopathologic patterns are most commonly associated with RA-ILD?
-UIP pattern on HRCT most commonly encountered, between 40-60% of cases.
-Histopathology usually correlates with HRCT. MC encountered histopathologic patterns are UIP, NSIP, OP
Aggregated data from multiple studies demonstrating the most common histopathologic patterns in CTD-ILDs. Note larger proportion of UIP in RA-ILD
-RA-ILD associated with UIP pattern has an increased risk of disease progression and death, and increased risk of flares compared with RA-ILD with NSIP pattern
Kaplan-Meier curve showing RA-ILD with UIP pattern; cumulative survival intermediate between RA-ILD with NSIP and IPF (another ILD characterized by UIP HRCT and histopath)
What is the role of antifibrotic therapy in non-IPF ILD?
– A recent trial (INBUILD – 2019) looked at nintedanib (antifibrotic FDA approved for IPF) in patients with non-IPF fibrosing interstitial lung disease (n=663) over 12 months of follow-up
Figure demonstrating the primary endpoint, decline in FVC over period of followup (188 mL in placebo versus 80 mL in nintedanib group).
-As a secondary endpoint, mortality was less in intervention group (11.5% placebo vs 8.1% nintedanib) although this was not statistically significant
– Since publication of INBUILD trial, FDA has approved use of nintedanib/Ofev for non-IPF progressive fibrosing ILDs
Finally, for a current and comprehensive review of the treatment of fibrosing interstitial lung disease including IPF and other progressive pulmonary fibrosis (PPF), make sure to check out a recent review in BMJ by our very own Gabby Liu, Scott Budinger and Jane Dematte!
An algorithmic approach to diagnosis and management
https://doi.org/10.1378/chest.09-0444
https://www.nejm.org/doi/full/10.1056/NEJMoa1908681
https://www.bmj.com/content/377/bmj-2021-066354