Improved Case of Bronchial Asthma by Re-administration of Pranlukast from Montelukast: Evaluation of Eosinophilic Inflammation in the Peripheral Airway

Background: Pranlukast and Montelukast are Cysteinyl leukotriene receptor antagonists with almost the same pharmacological activity. However, I will describe a case in which these drugs showed different therapeutic effects on clinical symptoms during the daytime and eosinophilic inflammation in the peripheral airway. Methods: A 70-year-old male patient with non-atopic bronchial asthma who was treated with 400 μg/day of Budesonide Turbuhaler® (BUD-TH) changed from Pranlukast (225 mg, twice daily) to Montelukast (10 mg, one tablet before sleeping), resulting in worsening clinical symptoms consisting of sputum and cough in the daytime, mainly at lunch time. Due to the fact that the symptoms did not improve sufficiently, instead of increasing the dose of BUD-TH, we investigated the clinical symptoms and pulmonary functions as well as measured the mean eosinophil count, eosinophil cationic protein (ECP) and eotaxin in the hypertonic saline-induced sputum prior to administration of Pranlukast, and 4 and 8 weeks after the re-administration of Pranlukast from Montelukast. Results: Following the re-administration of Pranlukast, the clinical symptoms disappeared within a few days and pulmonary function improved within 4 weeks. Eosinophils in the induced sputum almost completely disappeared for 4 weeks. The sputum ECP and eotaxin before and 4 weeks after the re-administration of Pranlukast changed from 700 μg/l to 192 μg/l, and 69.9 pg/ml to 30.6 pg/ml, respectively. After 8 weeks, no sputum induction was found. Conclusions: The clinical difference between these two similar antagonists may be caused by the time difference relating to when and how often each drug is administered, suggesting the existence of the lunchtime dip

Key points in effective inhaler technique training for asthma and COPD patients

Inhalation therapy involves two types of adherence: adherence to the drug and adherence to the procedures for the inhalation device. Recent increases in the range of inhaled medications available have expanded treatment options, while simultaneously resulting in more complicated treatments for patients due to the increasing diversity of inhalation devices. Patients with asthma and chronic obstructive pulmonary disease (COPD) are required to not only take the agent at the indicated dosage, but also use the inhaler device in the proper manner with correct procedures. This review presents eight key points for training patients with asthma and COPD in effective inhaler technique. These points can help to ensure a good balance of adherence to both the medication and the inhalation device, and thereby maintain disease control in clinical settings.</p

The Clinical Evaluation of the Acceptance of Fluticasone Propionate Diskus® by Older Japanese Patients with Bronchial Asthma

Background: Fluticasone propionate (FP) Diskus® is generally regarded as an easy to use and efficacious inhaled device. This study clinically evaluated whether its easy handling and inhalation process were affected by the aging factor or not, compared with those of the FP Diskhaler® and Beclomethasone dipropionate (BDP). Methods: Twenty-four elderly patients with stable moderate asthma (12 aged 65-74 years and 12 aged 75 years or older) who were accustomed to using the Diskhaler® were evaluated by measuring the required time for finishing one-time inhalation with the device, compared with 7 patients aged less than 65. Ten elderly patients (5 aged 65-74 years, and 5 aged 75 years or older), who used the BDP, were also similarly evaluated and compared with 8 patients aged less than 65. All subjects then switched to use with the Diskus® and the required time for finishing one-time inhalation was measured soon after and 2 weeks after the change. The patients' usage impressions were also questioned. Results: The mean required times (seconds) were significantly different between patients aged 75 years or older, and with patients less than 65 years of age; 45.8 ± 8.1 vs. 31.8 ± 12.3 (p = 0.046) in the BDP group, and 56.8 ± 25.3 vs. 33.3 ± 18.5 (p = 0.047) in the Diskhaler®, respectively. Soon after changing to the Diskus®, those times became insignificant in both groups. After 2 weeks, the required time for using the Diskus® was significantly shortened in all age groups. 50.0% patients in the BDP group and 79.2% in the Diskhaler® group finally chose the Diskus®. Conclusions: The FP Diskus® inhalation was not affected by the aging factor and all patients could quickly get accustomed to using it, suggesting its clinical efficacy for older patients

Hydrofluoroalkane-Beclomethasone Dipropionate Effectively Improves Airway Eosinophilic Inflammation Including the Distal Airways of Patients with Mild to Moderate Persistent Asthma as Compared with Fluticasone Propionate in a Randomized Open Double-Cross Study

Background: To evaluate whether hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) controls eosinophilic inflammation, including that in the distal airways, more effectively than fluticasone propionate (FP) Diskus®. Methods: Fifty patients with well-controlled mild to moderate persistent asthma using FP for more than 6 months were randomly assigned to FP and HFA-BDP groups, and the treatment regimens of the two groups were switched twice between FP and HFA-BDP in a double cross-over manner at 3-month intervals after 2-week washout periods. Evidence of eosinophilic inflammation in blood and induced sputum samples was assessed, together with pulmonary function testing and an Asthma-related Quality of Life Questionnaire (AQLQ) survey after each treatment period. Results: The peripheral blood differential eosinophil count and sputum levels of eosinophil cationic protein (ECP) showed reciprocal changes during the study periods in both groups. The blood differential eosinophil count was significantly lower during the HFA-BDP than during the FP treatment period in both the FP (p = 0.004) and the HFA-BDP (p = 0.020) group. The late-phase induced sputum ECP level was significantly decreased during the HFA-BDP treatment period in both the FP (p = 0.016) and the HFA-BDP group (p = 0.023). The significant elevation of surfactant protein D values in the late-phase sputum observed in both groups indicated that late-phase sputum was obtained mainly from proximal peripheral airways. Both symptom and activity limitation domains of the AQLQ in the HFA-BDP group significantly increased after switching from FP to HFA-BDP. There were no significant changes in pulmonary function indices in either group at any time during the study. Conclusions: HFA-BDP improved residual eosinophilic inflammation in asthmatic airways, including distal airways, more effectively than FP

Current Situation of Asthma Therapy by Allergists in Primary Medical Facilities in Japan

Background: To reduce deaths from asthma, further use of inhaled corticosteroids (ICS) in accordance with the guidelines is required. The present study was conducted because specialists are responsible for increasing the use of guidelines, but the current state of asthma care provided by specialists in primary clinical settings has not been clarified. Methods: In collaboration with five primary medical facilities throughout Japan, severity of asthma, contents of asthma therapy, and the implementation rate of pulmonary function testing and peak flow measurements were analyzed for 1007 outpatients ≥40 years old with stable bronchial asthma. In all patients, peak inspiratory flow (PIF) was measured during examination. Results: Either ICS or ICS/long-acting beta 2 agonist (LABA) was used in almost all patients with at least mild persistent asthma. Although treatments adhered to the guidelines, therapeutic steps did not match asthma severity in many patients with mild intermittent asthma. Large gaps existed between facilities that measure pulmonary function and PEF in daily clinical practice and those that do not. While mean PIF value for all subjects was well maintained at 102.0 ± 29.1 L/min, some patients may not have been able to inhale efficiently in terms of PIF (5.1% of Turbuhaler® users and 5.7% of Diskhaler® users). Conclusions: When stepping down asthma therapy, some confusion in policy may exist, leading to guideline mismatches. Differences in the implementation of pulmonary function and PEF measurements, as indicators for long-term management, need to be minimized among specialists. For maintaining effective inhalation, inspiratory flow should be periodically checked