Highlights from Gabby Liu’s BMJ State of the Art review on pulmonary fibrosis!

Amazing work by Gabby Liu (@gliunit, PCCM Fellowship Class of 2022) on this BMJ State of the Art Review: https://www.bmj.com/content/377/bmj-2021-066354

Advances in the management of idiopathic pulmonary fibrosis and progressive pulmonary fibrosis

Highlights from the review, kindly summarized for us by the author:

• Discusses the conceptualization and pathophysiology of progressive pulmonary fibrosis
• 2022 ATS/ERS/JRS/ALAT guidelines define how to identify progressive pulmonary fibrosis:
  • ILD dx other than IPF
  • Radiologic evidence of pulmonary fibrosis
  • Evidence of progression, defined as meeting at least two of three criteria within the previous year with no alternative explanation:

1. Absolute decline in FVC >/=5% predicted or absolute decline in DLCOc >/=10% predicted
2. Worsening respiratory symptoms
3. Radiologic evidence of progression

• Therapies in the pipeline for treatment of IPF, undergoing phase 3 clinical trials:
  • Recombinant human pentraxin 2 – rhPTX
    • Inhibits recruitment of monocyte derived alveolar macrophages to areas of fibrosis
  • Pamrevlumab
    • Anti-CTGF antibody
    • CTGF mediates tissue remodeling, acting downstream of TGF-beta
  • Inhaled treprostinil
    • Prostacyclin analog approved for treatment of PAH and pHTN associated with ILD
  • NAC among IPF patients with TOLLIP TT genotype
    • Tripeptide precursor of glutathione that has antioxidant effects
• 
• Treatment of inflammatory ILDs:
  • Only RCT data supporting immunosuppression comes from studies of patients with SSc-ILD
  • Tocilizumab is the only immunosuppressive drug approved by FDA for treatment of SSc-ILD
    • Based on FaSScinate and focuSSced trials
  • Cyclophosphamide (CYC) and MMF are not approved by FDA for treatment of SSc-ILD but use is supported by Scleroderma Lung Studies I and II
    • SLS I : CYC reduced decline in FVC compared to placebo
    • SLS II: MMF non-inferior to CYC
• Treatment of progressive pulmonary fibrosis:
  • Nintedanib, supported by 2 RCTs:
    • SENSCIS: patients with SSc-ILD, no evidence of disease progression required for enrollment
      • Nintedanib reduced rate of FVC decline compared to placebo
      • ½ of patients on MMF at enrollment, nintedanib effective regardless of MMF use
    • INBUILD: Patients with non-IPF progressive fibrosing ILD, not allowed to be on immunosuppression
      • Nintedanib reduced rate of FVC decline compared to placebo
  • Pirfenidone, data less robust, RCTs ongoing
• Emerging diagnostics:
  • Envisia genomic classifier can help differentiate UIP from non-UIP histologic patterns from transbronchial lung biopsy and lung cryobiopsy by recognizing transcriptomic signature of UIP

Great work, Gabby!