Soichiro Hozawa

Bronchial asthma is characterized by chronic airway inflammation, which manifests clinically as variable airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma may induce airway remodeling and become intractable. The prevalence of asthma has increased; however, the number of patients who die from it has decreased (1.3 per 100,000 patients in 2018). The goal of asthma treatment is to control symptoms and prevent future risks. A good partnership between physicians and patients is indispensable for effective treatment. Long-term management with therapeutic agents and the elimination of the triggers and risk factors of asthma are fundamental to its treatment. Asthma is managed by four steps of pharmacotherapy, ranging from mild to intensive treatments, depending on the severity of disease; each step includes an appropriate daily dose of an inhaled corticosteroid, which may vary from low to high. Long-acting β2-agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonists are recommended as add-on drugs, while anti-immunoglobulin E antibodies and other biologics, and oral steroids are reserved for very severe and persistent asthma related to allergic reactions. Bronchial thermoplasty has recently been developed for severe, persistent asthma, but its long-term efficacy is not known. Inhaled β2-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and other approaches are used as needed during acute exacerbations, by selecting treatment steps for asthma based on the severity of the exacerbations. Allergic rhinitis, eosinophilic chronic rhinosinusitis, eosinophilic otitis, chronic obstructive pulmonary disease, aspirin-exacerbated respiratory disease, and pregnancy are also important conditions to be considered in asthma therapy.

The involvement of platelet-activating factor (PAF) in bronchial hyperresponsiveness (BHR) in bronchial asthma has been controversial. To determine whether PAF is involved in BHR in humans, we carried out a randomized, double-blind, placebo-controlled, two-phase cross-over study on the effects of Y-24180, a potent, specific, orally active PAF receptor antagonist, on BHR to methacholine in patients with asthma. The subjects were 13 patients with extrinsic stable asthma. The provocative concentration of methacholine producing a 20% fall in FEV1 (PC20-FEV1) was measured as an index of BHR. Y-24180 (20 mg twice a day) or a placebo was orally administered for 2 wk, respectively. At the time of cross-over from the first treatment regimen to the second regimen, administration of the test drug was suspended for 2 wk. The methacholine challenge test was performed four times, before and after the first treatment period and before and after the second treatment period. Compared with the placebo, Y-24180 significantly (p = 0.005) improved the PC20-FEV1 value without carryover effect and period effect by analysis of variance. These results suggest that PAF is an important mediator involved in the BHR of bronchial asthma in humans.