Cromolyn, a New Hope for Limited Treatment of Neutrophilic Asthma: a Phase II Randomized Clinical Trial

Background: In this study, we aimed to determine the effects of cromolyn on the clinical outcomes and neutrophilic inflammation in patients with resistant cough-variant asthma. Materials and Methods: Patients with cough-variant asthma, with normal physical examination and spirometry results, were treated by inhaled corticosteroids, antileukotrienes, antibiotics, and proton-pump inhibitors according to the Global Initiative for Asthma (GINA) guidelines. Seventy patients, who were resistant to these treatments, were enrolled in this doubleblind randomized clinical trial. After randomization, eligible subjects received a cromolyn metered dose inhaler (MDI) or a placebo MDI, which was completely similar in appearance to the cromolyn inhaler. The primary outcomes included cough and Asthma Control Test (ACT) score. Results: Based on the findings, cough significantly decreased with cromolyn therapy, compared to the placebo group. Other clinical findings, including dyspnea, sputum production, and nocturnal symptoms, also improved. The ACT score significantly improved to a nearly normal level (23.53±2.25) in the cromolyn group. Moreover, fractional exhaled nitric oxide (FeNO) significantly decreased with cromolyn treatment (14±9.31 ppm after treatment vs. 28.88±27.39 before treatment). The neutrophil count significantly decreased in the cromolyn group (from 44±24.2% before the trial to 34.08±16.7% after the trial), while it increased in the placebo group (from 39.67±26.47% to 56.71±27.22%). Conclusion: Cromolyn improved the clinical findings of resistant cough-variant asthma and could suppress neutrophilic inflammation.