Idiopathic%20pulmonary%20fibrosis Treatment

Nintedanib

• A receptor blocker for multiple kinases
• Mediates the elaboration of fibrogenic growth factors:
  
  • Vascular endothelial growth factor receptors (VEGFR) 1-3
  • Fibroblast growth factor receptors (FGFR) 1-3
  • Platelet-derived growth factor receptors (PDGFR) 

• Its efficacy in idiopathic pulmonary fibrosis were evaluated in INPULSIS-1 & -2, a randomized, double-blind, placebo controlled, 52-week duration, phase III trial, with the rate of decline of forced vital capacity (FVC) in a patient with idiopathic pulmonary fibrosis significantly reduced at the end of the study

Pirfenidone

• A synthetic pyridone compound & an antibiotic agent that:
  
  • Inhibits the transforming growth factor beta (TGF-β)
  • Decreases the extracellular matrix
  • Blocks fibroblast proliferation in vitro 

• Recommended for patients with mild-to-moderate disease
• Slows the progression of lung impairment in patients with pulmonary fibrosis due to Hermansky-Pudlak syndrome
• Based on the 2 Clinical studies Assessing Pirfenidone in idiopathic pulmonary fibrosis 004 & 006 (CAPACITY), Pirfenidone reduced both all-cause & IPF-related mortalities at 52 weeks
• ASsessment of Pirfenidone to Confirm Efficacy aND safety of idiopathic pulmonary fibrosis (ASCEND) is a randomized, placebo-controlled, double-blind trial that was required by the US Food & Drug Administration (US FDA) to confirm its effectivity on disease progression showed a reduction in the decline of forced vital capacity at week 52 & a decrease by 43% to the risk of death
• The safety of both trials (ASCEND & CAPACITY) were both demonstrated

Systemic Glucocorticoids

• Recommended for confirmed idiopathic pulmonary fibrosis during acute exacerbations
• The given dose is tapered based on the severity of the disease & patient's response to therapy
  
  • In patients who responds to therapy, the dose is slowly tapered (weeks-months)
  • Patients are then closely followed-up & monitored, to ensure that there is no recurrence of the disease

Other Treatments

• Use of Ambrisentan, Warfarin, Imatinib, or combination Prednisone/Azathioprine/N-acetylcysteine for idiopathic pulmonary fibrosis is not strongly opposed by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, & the Latin American Thoracic Association
• Treatment with Sildenafil, Bosentan, Macitentan, or N-acetylcysteine monotherapy for idiopathic pulmonary fibrosis is not recommended but may be considered in special conditions
  
  • Some studies cited improvement in shortness of breath, quality of life, arterial oxygen saturation with Sildenafil use
  • Two studies reported improvements in 6MWT distance while other studies have not found any significant difference in patients given N-acetylcysteine monotherapy
  • Further studies are needed to weigh the use of Sildenafil, Bosentan, Macitentan, & N-acetylcysteine monotherapy in idiopathic pulmonary fibrosis

Home Pulse Oximetry

• It is noninvasive & is used to assess arterial oxygen saturation of hemoglobin (S_pO₂)
  
  • Light-absorbing variations from arterial blood flow pulsation are measured 

• Used for monitoring & maintaining of the S_pO₂ level to >90%
  
  • If maintained, the development of a secondary pulmonary hypertension would be prevented

Supplemental Oxygen Therapy

• Patients with acute exacerbation of idiopathic pulmonary fibrosis have a high oxygen requirement because they need to maintain a pulse oxygen saturation of >88%
• In patients with acute exacerbation of idiopathic pulmonary fibrosis, hypoxemia is treated with supplemental oxygen
  
  • This may be sufficient to treat dyspnea but they must be monitored regularly as dyspnea due to idiopathic pulmonary fibrosis may be refractory 

• Dyspnea upon exertion may be relieved by ambulatory or long-term oxygen therapy
• Long-term oxygen therapy is recommended for idiopathic pulmonary fibrosis patients with clinically significant resting hypoxemia
• Mechanical ventilation is not recommended for acute exacerbation of idiopathic pulmonary fibrosis

Pulmonary Rehabilitation

• It improves symptoms, capacity to do exercises (eg walking distance) & quality of life, & reduces the severity of dyspnea of patients with idiopathic pulmonary fibrosis
• The rehabilitation programs should be based on the severity of the disease

Clinical Trials

• Patients with idiopathic pulmonary fibrosis are encouraged to join & participate in clinical trials of emerging therapies
  
  • The ideal candidate for a clinical trial is a patient with mild to moderate idiopathic pulmonary fibrosis 

• Information about the trial will be provided for each patient & its assignment would depend on the patient’s assessment & condition