TO THE EDITOR
Interstitial lung disease (ILD) is a group of diffuse lung diseases affecting the interstitial, alveolar, and/or bronchioles, with numerous classifications and complex aetiologies. Among these, idiopathic pulmonary fibrosis (IPF) is the most common. Lei et al[1] have shown that timely initiation of pirfenidone treatment in individuals diagnosed with IPF can effectively reduce the occurrence of adverse reactions. IPF is a chronic, progressive, fibrosing interstitial pneumonia of unknown aetiology, characterised by progressive worsening of dyspnoea and lung function[2,3]. The prevalence of IPF appears to be increasing, although currently only 0.33-4.51 per 10000 people are affected[4]. The prognosis is grim, with an average life expectancy of 3–5 years from diagnosis if left untreated[5].
IPF
According to the 2022 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Asociación Latinoamericana de Tórax evidence-based guidelines, pirfenidone, a cellular multi-target drug first approved for the treatment of IPF in 2011. They slow the deterioration of forced vital capacity (FVC) and provide patients with greater comfort for longer periods[2]. In a post hoc analysis using data from the ASCEND and CAPACITY studies, King et al[6] demonstrated significant attenuation of FVC decline, risk of all-cause mortality, and respiratory hospitalizations with pirfenidone, particularly in the mild-to-moderate lung impairment stage. This study also highlights the potential benefits of early pirfenidone administration by comparing treatment outcomes among the early, late, and control groups. Therefore, based on available data in some areas of the world, the approval of pirfenidone for treatment does not include patients with advanced IPF. Recently, other researchers conducted studies comparing the effectiveness and safety of pirfenidone in patients with advanced IPF versus those with non-advanced IPF. The authors provided evidence that pirfenidone is effective and has an acceptable safety profile in patients with advanced IPF. For example, Behr et al[7] found that patients with advanced IPF who received pirfenidone had a lower rate of all-cause mortality than those who received placebo, and that the long-term treatment benefit of pirfenidone was in worsening lung function in patients with advanced IPF and those with non-advanced IPF. Therefore, every patient should be treated with pirfenidone as soon as they are diagnosed with IPF, regardless of disease progression.
However, IPF is often over-diagnosed in clinical practice. It is essential to diagnose IPF after carefully considering the clinical symptoms and imaging findings, and excluding other possible causes. Many patients with ILD from rural areas, where comprehensive investigations are lacking, are misdiagnosed as IPF and are prescribed pirfenidone for prolonged treatment. Consequently, they may miss the optimal window of opportunity to treat their underlying conditions such as rheumatoid arthritis, allergies, or coronavirus disease 2019, resulting in joint deformities or delayed recovery of lung function when they seek care at our clinic[8,9]. Therefore, an accurate diagnosis is crucial for IPF prognosis.
In addition, pirfenidone is expensive, incurs significant self-funded expenses, does not halt the overall progression of IPF, and has a high mortality rate within 3 years to 5 years of diagnosis[10]. Despite being well tolerated, pirfenidone often causes side effects such as rash, weight loss, nausea, and fatigue. There have been cases of liver dysfunction, particularly increased serum levels of alanine aminotransferase, aspartate aminotransferase and bilirubin[11]. Therefore, it is essential to regularly monitor liver function in patients taking pirfenidone. Exploring the different routes of administration of pirfenidone in IPF is crucial, given new insights into the pathogenesis of the disease. Inhaled pirfenidone can achieve higher drug concentrations in lung tissue at a lower dose than oral administration without causing respiratory and systemic adverse effects[12,13]. Further research is needed to investigate the potential synergistic benefits of new agents and routes of administration for IPF treatment.
CONCLUSION
To achieve optimal outcomes, active interventions should be initiated at every stage of IPF. The timely initiation of pirfenidone treatment has been shown to be effective in reducing the occurrence of adverse reactions in patients with IPF. Furthermore, the appropriate selection of pharmaceutical approaches or right timing for IPF treatment could be beneficial and requires further investigation.
