Novel treatment vision for respiratory diseases involving retinoic acid identified by University of Fukui led group

Sinusitis triggered by a cold or other illness is commonly called a sinus inflammation and causes pain, pressure, blocked olfactory tissues, retention of nasal discharge due to inflammation, and formation of nasal polyps. Because chronic conditions can lead to a decrease in quality of daily life and have serious consequences, nasal polyps are treated by surgically removing them. However, with cases of eosinophilic sinusitis, a designated incurable disease, half of the cases recur within five years after polyps are removed. This results in steroids being used, but side effects from their long-term use have become a problem. It is estimated that there are two million chronic sinusitis patients in Japan and new treatments are needed as 20,000 of those patients are considered intractable.

A research group led by Masafumi Sakashita and Tetsuji Takabayashi of the Faculty of Medical Sciences, University of Fukui, has discovered for the first time in the world that vitamin A, an essential vitamin for the body, and its metabolite, retinoic acid, are involved as one of the causes of eosinophilic sinusitis. "We want to link this to a new treatment method by administering retinoic acid," explained Sakashita. "We will conduct joint research with companies on a nasal administration method and are also considering physician-led clinical trials to confirm the appropriate volume." The group's findings were published in The Journal of Allergy and Clinical Immunology.

The University of Fukui research team has previously shown that nasal polyps are caused by deposits of fibrin and that patients with eosinophilic sinusitis have less tissue plasminogen activator (tPA) to degrade the fibrin. However, retinoic acid, an active metabolite of vitamin A, has been reported to induce tPA from vascular endothelial cells.

By examining nasal polyps from patients with eosinophilic sinusitis, the group's research revealed reduced gene expression of tPA, markedly less tPA protein, and less vitamin A and retinoic acid. Due to this, Sakashita thought that if this was the case, increasing tPA may lead to a treatment method, so the group cultured normal human airway epithelial cells to see if tPA increased by adding retinoic acid, and found that gene expression increased and tPA also increased. However, tPA decreased when IL13, which is increased in patients, was added. When IL13 and retinoic acid were added simultaneously, the retinoic acid was overcome and tPA increased.

Vitamin A and retinoic acid administered directly into the nasal cavity or taken internally may provide one more treatment option for refractory chronic sinusitis and may contribute to the prevention of recurrence after surgery. The researchers also aim to develop a simple method to measure retinoic acid and establish a biomarker to diagnose disease. "Taking a large amount of Vitamin A can lead to an overdose and side effects such as decreased liver function, so it's important to understand that taking large amounts of supplements or other substances will not help," cautioned Sakashita.