Daily Archives: July 12, 2022

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

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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!