Management of patients with fibrosing interstitial lung diseases

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose This article summarizes the appropriate use and pharmacology of treatments for fibrosing interstitial lung diseases, with a specific focus on the antifibrotic agents nintedanib and pirfenidone. Summary The interstitial lung diseases are a heterogenous group of parenchymal lung disorders with a common feature—infiltration of the interstitial space with derangement of the normal capillary-alveolar anatomy. Diseases characterized by fibrosis of the interstitial space are referred to as the fibrosing interstitial lung diseases and often show progression over time: idiopathic pulmonary fibrosis is the most common fibrotic interstitial lung disease. Historically, therapies for fibrosing lung diseases have been limited in number, questionable in efficacy, and associated with potential harms. Food and Drug Administration (FDA) approval of the antifibrotic agents nintedanib and pirfenidone for idiopathic pulmonary fibrosis in 2014 heralded an era of reorganization of therapy for the fibrotic interstitial lung diseases. Subsequent investigations have led to FDA approval of nintedanib for systemic sclerosis–associated interstitial lung disease and interstitial lung diseases with a progressive phenotype. Although supportive care and pulmonary rehabilitation should be provided to all patients, the role(s) of immunomodulators and/or immune suppressing agents vary by the underlying disease state. Several agents previously used to treat fibrotic lung diseases (N-acetylcysteine, anticoagulation, pulmonary vasodilators) lack efficacy or cause harm. Conclusion With the introduction of effective pharmacotherapy for fibrosing interstitial lung disease, pharmacists have an increasingly important role in the interdisciplinary team managing these patients.

Association of rs3750920 polymorphism in TOLLIP with clinical characteristics of fibrosing interstitial lung diseases in Japanese

TOLLIP polymorphism has been implicated in the development and prognosis of idiopathic pulmonary fibrosis (IPF), mainly in whites. However, ethnic differences in the characteristics of other interstitial pneumonia (non-IPF) subtypes are unclear. We evaluated the association between the rs3750920 genotype and the clinical characteristics of Japanese patients with fibrosing interstitial lung diseases (ILD). We genotyped 102 patients with fibrosing ILD (75 IPF and 27 non-IPF patients) and analyzed the interaction between the rs3750920 genotype distribution and their clinical characteristics. The overall frequencies of the C/C, C/T, and T/T genotypes were 69%, 25%, and 6%, respectively. The proportion of minor T allele carriers was larger in IPF patients than in non-IPF patients (37% vs. 15%, P = 0.031). In addition, survival at 3 years was significantly better for carriers than for non-carriers of the T allele. There was no significant association between genotype distribution and change in pulmonary function after introduction of antifibrotic agents. The frequency of the minor T allele of rs3750920 was low in Japanese patients with fibrosing ILD, particularly in non-IPF patients. Carriers of the minor T allele had better survival than non-carriers. Presence of the T allele might thus be an indicator of better outcomes for fibrosing ILD.

Antifibrotic drugs for COVID-19: From Orphan drugs to Blockbusters?

: Antifibrotic agents are known to treat idiopathic pulmonary fibrosis. The two antifibrotic agents approved and in usage are Pirfenidone and Nintedanib granted by the USFDA in 2014. They are both known to decrease inflammation in the lungs. The fact that COVID-19 has shown to cause inflammation and fibrosis in the lungs frames the theory of their usage in the treatment of the disease by reducing lung scaring and allowing faster discharge of patients with post-COVID complications. The need for them to change their status from orphans to blockbusters has not happened yet due to fewer data and less research available on them as well as various other economic and patient-related factors. Since COVID-19 is widespread and causes many complications of the lungs that are similar to what these two drugs treat. We believe that the status of these drugs could be changed due to an increase in demand for them.