RESUMO
BACKGROUND AND PURPOSE: Itraconazole therapy has been reported to control asthma in severe therapy-resistant asthma with fungal sensitization. The aim of this study was to investigate the impact of anti-fungal therapy on the treatment of severe asthma, irrespective of sensitization. MATERIALS AND METHODS: This active comparator clinical trial was performed on 110 therapy-resistant asthmatic patients who were randomly assigned into two groups of case and control. The patients in the case group were administered 200 mg itraconazole twice a day and the control group received 10 mg prednisolone after breakfast for 4 months. The asthma control test (ACT) which was used as a marker for the global evaluation of treatment effectiveness (GETE) was applied as the primary endpoint parameter. Cough, dyspnea, and sleep disturbance were measured on a scale of 1-4, with 1 representing no symptom and 4 indicating severe exhausting disturbance. RESULTS: Based on the obtained results, 71% of the itraconazole group demonstrated a marked improvement in the GETE score after a four-month treatment. Itraconazole was able to suppress clinical symptoms, including cough, dyspnea, and night symptoms, and their physical exam was indicative of normalization in 60% of the patients. On the other hand, the patients in the parallel group "prednisolone" were only able to control dyspnea. The ACT score represented a notable improvement with itraconazole (mean: 14 before the trial and >20 after the trial) and spirometry parameters underwent a considerable change from obstructive pattern to normal. Furthermore, adverse effects were only detected in 6% of itraconazole users. CONCLUSION: The results of this clinical trial indicted the effectiveness of antifungal therapy for the control of the clinical condition of a subgroup of patients with severe steroid-refractory asthma.
RESUMO
Our study aimed to assess the influence of common methylprednisolone therapy on innate inflammatory factors in potential brain-dead organ donors (BDDs). The study groups consisted of 50 potential BDDs who received 15 mg/kg/d methylprednisolone and 25 live organ donors (LDs) as control group. Innate immunity gene expression profiling was performed by RT-PCR array. Soluble serum cytokines and chemokines, complement components, heat shock protein 70 (HSP70) and high mobility group box-1 (HMGB1) were measured by ELISA. Surface expression of TLR2 and TLR4 were determined using flow cytometry. Gene expression profiling revealed up-regulation of TLRs 1, 2, 4, 5, 6, 7 and 8, MYD88, NF-κB, NF-κB1A, IRAK1, STAT3, JAK2, TNF-α, IL-1ß, CD86 and CD14 in the BDD group. Remarkably, the serum levels of C-reactive protein and HSP70 were considerably higher in the BDD group. In addition, serum amounts of IL-1ß, IL-6, TNF-α, HMGB1, HSP70, C3a and C5a, but not IL-8, sCD86 or monocyte chemoattractant protein-1, were significantly increased in the BDD group. Significant differences were observed in flow cytometry analysis of TLR2 and TLR4 between the two groups. In summary, common methylprednisolone therapy in BDDs did not adequately reduce systemic inflammation, which could be due to inadequate doses or inefficient impact on other inflammatory-inducing pathways, for example oxidative stress or production of damage-associated molecules.