ILD roundup 8/12/22

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 

https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-group-progressive-interstitial-lung-diseases 

 

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