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Itraconazole as a treatment for severe persistent asthma results in a reduction in bronchial wall thickness and an improvement in symptoms and pulmonary function.

Severe persistent asthma (SPA) represents five to ten percent of the total asthma population. Long-term use of inhaled corticosteroids in SPA can result in fungal colonization and inflammation. Various inflammatory mediators can, over time, induce airway remodeling, characterized by changes like smooth muscle hypertrophy, fibrosis, neovascularization, and wall thickening. Increased airway wall thickness is associated with severe asthma symptoms and decreased pulmonary function. 

A study published in the Iranian Journal of Allergy, Asthma, and Immunology has demonstrated that the antifungal medication itraconazole effectively reduces bronchial wall thickness and improves symptoms and pulmonary function tests in SPA.

Study Design and Population

The study was a randomized, double-blind, placebo-controlled clinical trial. A total of 75 SPA patients were assessed after eight months of treatment with itraconazole, prednisolone, or placebo, along with standard asthma controllers. The wall thickness of the right upper lobe apical segmental bronchus (RB1) was measured using high-resolution computed tomography. Baseline characteristics were similar among the groups.

Significant Reduction in RB1 Wall Thickness and Area Observed 

Treatment with itraconazole resulted in a significant reduction in RB1 wall thickness and wall area. The wall thickness percentage decreased from 46% pre-treatment to 43.7% post-treatment. Wall area percentage and ratios of wall thickness to body surface area and wall area to body surface area were also significantly reduced by the end of the treatment. No significant change in these parameters was observed in the other groups. A significant increase in airway lumen caliber, indicated by mean inner radius and lumen area compared to body surface area, was observed in both itraconazole and prednisolone groups.

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Significant Improvement in Dyspnea and Wheeze 

In the itraconazole group, 13 patients showed improvement in dyspnea after treatment, which was significantly greater than in the prednisolone and placebo groups, with improvement in 9 and 2 subjects, respectively. Many patients with wheeze improved after itraconazole treatment (13 out of 23). No significant change in wheezing was observed in the other groups, with improvement in 6 out of 24 and 2 out of 23 in the prednisolone and placebo groups, respectively. Additionally, the Asthma Control Test (ACT) score significantly improved after treatment with itraconazole (from 11.3 to 16.5) as compared with the prednisolone (from 11.5 to 14) and placebo (from 10.9 to 11.6) groups.

Fractional Exhaled Nitric Oxide and Spirometry Results

The median fractional exhaled nitric oxide (FeNO) significantly reduced from 31 to 23 and 35 to 27 after treatment in the itraconazole and prednisolone groups, respectively. No significant change was noted in the placebo group.

Improvement in Pulmonary Function Tests With Itraconazole and Prednisolone Treatment

Comparison of pulmonary function tests before and after treatment demonstrated that patients who received itraconazole showed significant improvement in forced expiratory flow (FEF) at 25–75% of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC. The prednisolone group also showed significant post-treatment improvement in spirometry parameters. No significant change was observed in the placebo group.

Source

Farnaz, A., Majid, M., Mohammadamin, S., Shadi, G., Mohammad Sarafraz, Y., Saeed, N., & Amirhossein Hashemi, A. (2023). Itraconazole Improved Bronchial Wall Thickness in Severe Persistent Asthma: A Double-blind Placebo-controlled Randomized Clinical Trial. Iranian Journal of Allergy, Asthma and Immunology, 22(1). https://doi.org/10.18502/ijaai.v22i1.12000

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