Dry Powder and Budesonide Inhalation Suspension Deposition Rates in Asthmatic Airway-Obstruction Regions.

Steroid inhalation is the standard bronchial asthma therapy and it includes powdered metered doses, dry powder, and nebulizer suspension. However, particle sizes vary widely. The research goal was to demonstrate that different budesonide administration forms and devices have various deposition rates in the airway obstruction region. Here, we compared relative inhalation therapy efficacies and identified therapies that delivered the highest drug doses to the airway obstruction region. Weibel's anatomy data were used to identify the airway obstruction region in asthma. Based on European Standardization Committee data, we investigated the diameters of the drug particles being deposited there and evaluated the average particle size and distribution of the budesonide dosage forms and application devices. Drug dose depositions were measured by HPLC at each stage of a Cascade Impactor. Weibel's anatomy data indicated that the 1st-4th bronchial generations comprised the airway obstruction region and corresponded to the tracheobronchial area. According to the European Standardization, particles 2-6 µm in diameter were readily deposited there. The proportions of particles in this size range were 33.0%, 32.0%, 59.0%, and 78.0% for Turbuhaler, Symbicort, mesh-type NE-U22 suspension, and jet-type NE-C28 suspension, respectively. We localized the airway obstruction regions of bronchial asthma and identified the optimal inhalation therapy particle size. An electric nebulizer was more efficacious for budesonide administration than dry powder delivery. The NE-C28 treatment deposited 2.36x more budesonide in the airway obstruction region than dry powder delivery systems.

10-Year Follow-Up of Frequently Relapsed Chronic Eosinophilic Pneumonia Starting at 15 Years Old; Attempts to Treat with Inhaled Corticosteroid (A Case Report).

BACKGROUND Eosinophilic pneumonia is recognized both as an eosinophil-associated disease and as bronchial asthma. In eosinophilic pneumonia, the site of eosinophilic infiltration is mainly the alveolus and the peripheral airway; the disability of pulmonary function is restrictive, as opposed to from bronchial asthma, which has a relatively central side bronchus region and obstructive function. Differences in inflammatory region and the activation degree of T-cell and eosinophil parameters were predicted. CASE REPORT To determine the extent of inflammation and the region showing the inflammation in eosinophilic pneumonia, parameters like HLADRCD4/CD4 (%), CD25CD4/CD4 (%), ECP, soluble IL2R, and IL5 were examined in BALF and in peripheral blood during the active phase and remission phase. The percentage of HLADRCD4/CD4, IL-5, and the percentage of CD25CD4/CD4 were extremely high during the acute phase in BALF as compared to that in peripheral blood during the active and the remission phase. To avoid the adverse effects of systemic administration of steroids, we tried 5 different kinds of steroid through inhalation. We used%FVC by spirometry as a parameter to determine the recurrence of the disease. However, the inhaled steroids could not control the remission for long. This is the first report in which frequent recurrence of the disease was seen despite treatments and in which%FVC was used to determine the disease condition. CONCLUSIONS The principle site of inflammation in eosinophilic pneumonia is the peripheral bronchus and the alveolar area. Percent FVC can be a useful parameter for assessment of recurrence of the disease. In the present case, the disease could not be kept under control despite treatment with 5 different steroids through the inhalation route.

Data on nasal eosinophil positive rates in childhood asthma on each age.

Nasal eosinophil examination is routine for the diagnosis of nasal eosinophil-positive rhinitis in patients with rhinorrhea symptoms. This retrospective data investigated whether testing for nasal discharge eosinophils is useful for diagnosing childhood allergic asthma, and changes of positive rates by each age. Infants and young children (n = 180) with at least 3 recurrent episodes at intervals of ≥ 1 week of respiratory symptoms and bronchodilator inhalation improvements, were divided into an asthma group and a non-asthma group, and the presence or absence of nasal discharge eosinophils was examined by age. Correlations between nasal discharge eosinophils and other predictive factors for persistent asthma were also examined. The evaluation of nasal discharge eosinophils in the asthma group showed a significantly high positive rate in older age groups than in the 0-1-year-old age group (p< 0.05-0.001). However, none of the asthma patient groups had any significant changes between the 0-1-year-old group and older groups. This pattern was similar for other risk factors, showing correlations between nasal discharge eosinophils and other predictive factors.

Data on substantial gravity of carbon dioxide due to pressured metered-dose inhaler steroid treatments for the 2006 year in Japan.

People all over the world should work in each individual against global warming due to greenhouse gas that is made up of a majority of carbon dioxide. On the other hand chloro-fluoro-carbon (CFC) was used with pressured metered-dose inhaler steroid therapy, but CFC became banning the use because of ozone depleting substance. Hydrofluorocarbon (HFA134a, tetra-fluoro-methane) is used as alternative CFC until now. Less-famously hydro-fluoro-carbon (HFA134a) have 1300-fold (mole ratio) energy of heat-trapping relative to carbon dioxide. On an extremely localized story, we derived substantial gravity of carbon dioxide from sales total of pressured metered-dose inhaler (pMDI) steroid drugs for the year in Japan. The amount of total sales of inhaled corticosteroid drugs on annual 2006 year was 320 hundred-millions yen. 88 hundred-millions yen (27.4% for total ICS sales) was accounted for pressured metered-dose inhaler steroid. Now in Japan there are three kinds of pressured metered-dose inhaler steroid drugs which all use tetra-fluoro-methane (HFA134a). In fact total gravity of tetra-fluoro-methane (HFA134a) from pressured metered-dose inhaler steroid for annual 2006 year was 19.7 t and substantial gravity of carbon dioxide was 10.8 thousand ton. As total gravity of carbon dioxide production throughout the year in Japan was 13 hundred-million ton. Therefore substantial gravity of carbon dioxide by steroids pressured metered-dose inhaler was very small (0.001%) compared to total carbon dioxide production in Japan. Until today carbon-dioxide reducing make very slow progress, for that reason medical service worker unexceptionally should exert an effort for carbon-dioxide reduction if only slightly through the daily clinical examination.

Data on various allergen specific IgEs and prospective treatments on food-dependent exercise-induced anaphylaxis.

Food-dependent exercise-induced anaphylaxis (FDEIAn) is an anaphylactic reaction induced by physical exercise after ingestion of certain meals. FDEIAn is not very frequent, but recent case reports associated with various meals indicate an upward trend. Here, we report the data of various food specific IgEs and the clinical course of an experience with a patient who exhibited a unique FDEIAn reaction. Various food specific IgEs including staple food were positive with high levels. We could not find out the cause food of FDEIAn. Therefore we started preventive drug treatment. Specifically, only the skin symptoms (urticaria) were prevented by administering anti-histamine (hydroxyzine) daily, and respiratory symptoms (wheezing and distress) were prevented by daily administration of a leukotriene receptor antagonist (montelukast).

Comparison of the Clinical Efficacy of Salbutamol with Jet and Mesh Nebulizers in Asthmatic Children.

BACKGROUND: Ultrasonic, jet, and mesh nebulizers have all been used in the treatment for asthma. Mesh nebulizers reportedly offer the best inhalation efficiency. METHODS: This study aimed to clarify the utility of the mesh nebulizer, compared to jet nebulizers, in the treatment of pediatric asthma patients. Participants included 88 children <6 years old who were receiving treatment for asthma at Murayama Pediatric Clinic. Heart rate, peripheral oxygen saturation in arterial blood, and Mitsui symptom scores were compared before and after treatment with a mesh nebulizer (n = 43) or jet nebulizer (n = 45) using a salbutamol inhalation solution (0.2 ml for children ≧ 2 years old, n = 51; 0.1 ml for children < 2 years old, n = 37). RESULTS: Other than required inhalation time, clinical findings did not differ between mesh and jet groups. In both groups, heart rate increased significantly in patients treated with 0.2 ml (1000 microg) of salbutamol. CONCLUSIONS AND CLINICAL RELEVANCE: The required inhalation time of the mesh nebulizer was superior to the jet nebulizer. Children ≧ 2 years with mild asthma attacks experienced a significantly increased heart rate in both groups. The dose of salbutamol (0.2 ml for ≧2 years) used for asthma attacks should be reconsidered in mild asthma.

Inhaled steroid inhibits development of total and mite IgE.

Serum levels of total immunoglobulin E (IgE) and allergen-specific IgE are related to asthma severity and risk factors for persistent asthma in childhood wheezing. Inhaled corticosteroids (ICS) have been the most effective therapy in children with asthma, as well as in adults. The serum levels of total and mite specific IgE in children with asthma and the effects on IgE levels of beclomethasone dipropionate (BDP) treatment on IgE levels in asthmatic children were investigated. First, a cross-sectional study of 255 children with asthma was carried out to measure IgE levels. Children under three years of age with asthma who were negative for Df-specific IgE were then treated with BDP or disodium cromoglycate (DSCG) as controls for one year. Serum IgE levels, numbers of eosinophils in peripheral blood and clinical variables were determined before and after treatment. After one-year DSCG treatment, the total IgE levels increased significantly, whereas the levels remained the same during BDP treatment. Five of 22 (23%) patients in the DSCG-treated group became positive for Df-specific IgE; however, only one of 13 (8%) in the BDP-treated group became positive. Taken together, ICS therapy may modulate the levels of total IgE and allergen-specific IgE.

Nasal Discharge Eosinophils in Childhood Asthma Patients as a Predictive Factor for Persistent Asthma.

OBJECTIVE: Eosinophilic inflammation is thought to play a role in childhood asthma. Thus, examination of nasal eosinophils, instead of sputum, may be useful for the diagnosis of not only eosinophil-positive rhinitis but also persistent asthma. Nasal eosinophil examination is a routine for the diagnosis of nasal eosinophil-positive rhinitis in patients with rhinorrhea symptoms. This retrospective study investigated whether testing for nasal discharge eosinophils is useful for diagnosing childhood allergic asthma and whether nasal discharge eosinophils are predictive of persistent asthma. METHODS: Infants and young children (n = 180) with at least 3 recurrent episodes of respiratory symptoms and bronchodilator inhalation improvements at intervals of ≥1 week were divided into the asthma group and the nonasthma group, and the presence or absence of nasal discharge eosinophils was examined by age. Correlations between nasal discharge eosinophils and other predictive factors for persistent asthma were also examined. RESULTS: The evaluation of nasal discharge eosinophils in the asthma group showed a significantly higher positive rate in older age groups than in the 0-1-year-old age group (p < 0.05-0.001). However, none of the asthma patient groups had any significant changes between the 0-1-year-old and older groups. This pattern was similar for other risk factors, showing correlations between nasal discharge eosinophils and other predictive factors. CONCLUSIONS: Testing for nasal discharge eosinophils with asthma symptoms increases with age. Nasal discharge eosinophils with asthma symptoms may be a predictive factor for persistent asthma. This trial is registered with UMIN Clinical Trials (registration number UMIN000030776).

Deposition Dosages of Three Cromolyn Forms by Cascade Impactor.

Among inhaled asthma therapies, the present study aimed to identify factors for selecting the type of inhalation therapy for asthma. Three methods are used to deliver inhaled cromoglycate, and the airway deposition rate was evaluated using a cascade impactor with 3 dosage forms: dry powder (DP), pressurized metered dose inhaler (pMDI), and solution (jet- and mesh-types). The percentage of particles with diameters of 2-6 µm was 17.0% for the capsule, 51.8% for pMDI, 49.0% for jet-type NE-C28, and 40.4% for mesh-type NE-U22. The amounts of drug deposited in the bronchi were based on the particle distribution of the various dosage forms: 3.4 mg for the capsule, 1.0 mg for pMDI, 9.8 mg for one solution (jet-type NE-C28), and 8.1 mg for the other solution (mesh-type NE-U22). Jet-type or mesh-type electric nebulizers delivered 2-3 times more of the drug than capsules, and, compared with pMDI, 8-9 times more of the drug was deposited in the bronchi/bronchioles. Electric nebulizers are considered the best method. This study suggests that the size of particles deposited at sites of obstruction is larger than previously reported, and no obstruction of small airways occurs (<2 mm).

[Persistence rate for clinic visit in children with asthma after initiating controller therapy].

OBJECT: To investigate the actual condition of the persistence rate for clinic visit in children with asthma requiring controller medication. METHODS: Seventy-three asthma children (0 to 15 years of age) who initiated controller medication were enrolled this study. Patients and their parents were educated about this disease (mechanism of asthma, airway inflammation, and necessity of asthma medication) and instructed to visit clinics regularly every 30 days. We prospectively monitored visit rate of the patients for 180 days. RESULTS: Mean persistence rate for clinic visit of all patients was gradually decreased, 90.4% on the 30 day, 82.2% on the 60 day, 78.1% on the 90 day, 67.1% on the 120 day and 38.4% on the 180 day, respectively. The persistence rate on the 180 day of 2 to 5 years old patients was significantly lower than that of < 2 years old patients and the rate on the 60 days or more after in 6 to 15 years old patients was lower than that of < 2 years old patients. It was also significantly lower in patients with moderate and severe persistent asthma than in mild persistent patients. CONCLUSION: Despite of the investigation in the setting of asthma specialty clinic, the persistence rate for clinic visit was decreased with time, especially in 6 to 15 years old or moderate to severe asthmatic patients. In order to improve the situation, it is necessary to analyze the cause of poor adherence and make a concrete action plan.