What is pulmonary fibrosis and how is it managed?

From the Guidelines

Pulmonary fibrosis is a chronic lung disease that requires a comprehensive management approach, including pharmacological and nonpharmacological therapies, to slow disease progression, relieve symptoms, and improve quality of life, as outlined in the 2022 clinical practice guideline by the ATS/ERS/JRS/ALAT 1. The management of pulmonary fibrosis involves a multifaceted approach, including:

• Pharmacological therapies, such as nintedanib and pirfenidone, to slow lung function decline
• Nonpharmacological therapies, including oxygen supplementation and pulmonary rehabilitation, to improve symptoms and quality of life
• Evaluation and treatment of existing comorbidities, such as pulmonary hypertension, gastroesophageal reflux, obstructive sleep apnea, and lung cancer
• Involvement of palliative care to help with symptom management, including cough, dyspnea, and anxiety
• Patient values and preferences should be explored, and patients at increased risk of mortality should be referred for lung transplantation at diagnosis. According to the 2022 guideline, patients should be evaluated every 3-6 months or more often for disease progression, and acute exacerbations may be treated with corticosteroids 1. Key aspects of pulmonary fibrosis management include:
• Slowing disease progression with antifibrotic medications
• Relieving symptoms, such as cough and dyspnea, with oxygen therapy and pulmonary rehabilitation
• Improving quality of life through comprehensive care, including palliative care and management of comorbidities
• Regular follow-up with pulmonologists to monitor disease progression and adjust treatment accordingly, as recommended in the 2022 guideline 1.

From the FDA Drug Label

The efficacy of pirfenidone was evaluated in patients with IPF in three phase 3, randomized, double-blind, placebo-controlled, multicenter trials (Studies 1,2, and 3) Study 1 was a 52-week trial comparing pirfenidone 2,403 mg/day (n=278) versus placebo (n=277) in patients with IPF. In all three trials, over 80% of patients completed study treatment A total of 1,247 patients with IPF were randomized to receive pirfenidone 2,403 mg/day (n=623) or placebo (n=624) in these three trials.

Pulmonary fibrosis, specifically Idiopathic Pulmonary Fibrosis (IPF), is a condition where the lungs become scarred, leading to breathing difficulties.

• Management of IPF includes treatment with pirfenidone, which has been shown to reduce the decline in forced vital capacity (FVC) in patients with IPF 2.
• The treatment effect of pirfenidone was evaluated in three phase 3 trials, which demonstrated a statistically significant reduction in the decline of FVC in patients receiving pirfenidone compared to placebo.
• However, all-cause mortality did not show a statistically significant difference between pirfenidone and placebo in these trials.

From the Research

Definition and Symptoms of Pulmonary Fibrosis

• Pulmonary fibrosis is a progressive, irreversible lung disease characterized by gradual thickening and scarring of lung tissue, impairing oxygen transfer into the bloodstream 3.
• Symptoms of pulmonary fibrosis include shortness of breath, fatigue, and a persistent dry cough 3.
• The disease can affect any age group, but it predominantly affects patients who are above 50 years of age, and the reasons are also related to smoking, pollution, and inhalation of harmful elements 4.

Management and Treatment of Pulmonary Fibrosis

• The FDA-approved antifibrotic agents Pirfenidone and Nintedanib can slow the progression of the disease, but they cannot completely stop the loss of lung function and do not provide a significant improvement in the quality of life of patients 3.
• Novel management strategies for idiopathic pulmonary fibrosis include targeting novel pharmacologic pathways, improving comorbidity management, and aiming for improved quality of life 5.
• Supportive care with pulmonary rehabilitation, oxygen therapy, and palliative care remain integral at various stages of the disease course, and lung transplant is the only lifesaving intervention for patients with end-stage fibrosis 5.
• Patients and providers should participate in shared decision-making when starting antifibrotic therapy, taking into consideration the benefits of treatment in addition to drug-related side effects and dosing schedules 6.

Comparison of Nintedanib and Pirfenidone

• Both nintedanib and pirfenidone have side effects that affect different patients in different ways and with different levels of severity, making the treatment even more challenging for medical practitioners 4.
• The nintedanib group had more frequent adverse drug reactions (ADRs) related to gastrointestinal and hepatobiliary disorders, while the pirfenidone group had more ADRs related to skin, nervous system, and vascular disorders 7.
• Independent variables that significantly increased the likelihood of experiencing ADRs were drug change, treatment type, gender, and age 7.

Future Directions

• Future investigation should aim to prevent the initial insult or injury that engages the multiple pathways associated with the development and progression of IPF, and targeted therapies represent just one management aspect with a multidisciplinary approach necessary for the global holistic care of these complex patients 5.
• Further research is needed to establish the etiology of IPF and to establish treatments that can stop its progression, and to optimize personalized therapies and patient outcomes 4, 7.