Type Of Inhaler Device Research Articles

Effects of inhaled steroids on growth, bone metabolism and adrenal function

Inhaled corticosteroids are a first-line therapy for persistent asthma in children. Major safety concerns of long-term inhaled corticosteroid therapy include suppression of adrenal function, growth and bone development. Proper interpretation of inhaled corticosteroid safety studies requires knowledge of the differences among various inhaled corticosteroid drug/delivery device systems. Dosage, type of inhaler device used, patient technique and characteristics of the individual drug influence the systemic effects of inhaled corticosteroids. Systemic side effects can occur when continuous high-dose treatment is required for severe asthma or when the dosage prescribed is excessive and compliance unusually good. Overall, however, recent studies confirm that benefits of inhaled corticosteroids, properly prescribed and used, clearly outweigh not only their potential adverse effects, but also the risks associated with poorly controlled asthma.

Promising ternary dry powder inhaler formulations of cromolyn sodium: Formulation andIn vitro-In vivo evaluation

Glucose monohydrate and sorbitol were evaluated as alternative carriers to á-lactose monohydrate in dry powder inhalations. Cromolyn sodium (CS) - carrier binary formulae were prepared and tested in vitro by aerosolization via a twin stage impinger using three types of inhaler devices; Spinhaler, Aerolizer and Handihaler. Glucose monohydrate and sorbitol-containing formulae that were inhaled via a Handihaler showed significantly higher drug fine particle fractions (P<0.001) than that of the same formulae aerosolized via other devices. Upon storage of the prepared formulae under uncontrolled humidity, that may be encountered during storage and use, marked reductions in these fractions were observed. Incorporation of an optimum Aerosil 200 concentration, as a ternary component, minimized this effect. A urinary excretion pharmacokinetic method was used to evaluate the bioavailability of the selected ternary formulae, inhaled via a Handihaler, relative to the marketed Intal Spincaps, inhaled via a Spinhaler. It was found that the relative bioavailability percentages of the developed formulae were more than twice that of the marketed one suggesting possible future utilization of these more effective ternrry formulae using the more efficient Handihaler inhaler device.

The gap between evidence-based medicine and daily practice in the management of paediatric asthma. A pharmacy-based population study from The Netherlands

We evaluated the adherence to national guidelines for the treatment of asthma in childhood. Prescriptions for anti-asthma medication for children (0-14 years of age) were retrieved from the InterAction DataBase (IABD) for the year 2002. These were compared with recommendations found in national guidelines. Anti-asthma medication was prescribed for 3,612 children (5%) of the paediatric population. Inhaled medication was prescribed for 3,554 (98%) children. In 1,940 of 1,993 (97%) of the children under the age of 6 years pressurised metered dose inhalers (pMDIs) were given. Short-acting beta2-agonists had not been prescribed in the previous 2-year period in 559 children (15%), 543 children older than 8 years (36%) did not receive a prescription for a dry powder inhalator and 239 children (7%) had more than one type of inhalator. Long-acting beta2-agonists were prescribed in 396 children, but without concomitant inhaled corticosteroids (ICS) in 35 children (9%). Inhalation therapy as the method of choice in asthma therapy and the use of pMDI in preschool children are widely accepted in the Netherlands. Not all children have been prescribed bronchodilators. Some children have more than one type of inhaler device and others use long-acting beta2-agonists not in combination with ICS. Although national and international guidelines about the treatment of asthma in children offer evidence-based advice, important principles are not followed. Effective interventions aimed at implementing existing guidelines into daily practice are urgently needed.

Comparative Study of Different Inhaler Devices in Asthmatic Children

The inhaler is an important drug delivery system in the treatment of asthma, but inhaler technique is often inadequate. We assessed technique in children diagnosed with asthma, comparing the performance of three devices. In a cross-sectional survey, 523 children (271 boys, 252 girls, ages 5 to 12 years; mean+/-SD 7.53+/-1.79 years) demonstrated inhalation technique according to Netherlands Asthma Foundation criteria during a first visit to a primary care clinic in Abha, Saudi Arabia. Patients used the device with which they were most familiar (either pMDI, Turbuhaler or Diskus). Two hundred children (38% of total population) used a pMDI, while 323 (62% of total population) used one of the dry powder inhalers 173 (58%) the Turbuhaler and 150 (47%) the Diskus. Only 49 children (25% of the total population) completed the assessment without making a mistake. The remaining 474 (75% of the total population) performed one or more manuevers poorly. Only 80 children who used an MDI (40% of those using the device) completed 50% or more of the maneuvers correctly compared with 111 (69% of those using the device) and 100 (67% of those using the device) of those using the Turbuhaler and Diskus, respectively (P=0.001 for comparison of MDI with dry powder inhalers). Children whose mothers had intermediate school or higher education performed better than those whose mothers had less education (P=0.001). The father's education had no bearing on performance with the inhaler. The inhaler technique of most asthmatic children is poor, but technique is better in children who use a dry powder compared a metered-dose inhaler. The level of the mother's education is positively associated with better inhalation technique in the child.

Expected characteristics of an ideal, all-purpose inhaled corticosteroid for the treatment of asthma

Background: Inhaled corticosteroids (ICSs) are well established as the mainstay of asthma therapy. A number of ICSs are now available, each with unique pharmacokinetic/pharmacodynamic profiles and physical characteristics. Objective: This article reviews the key characteristics of an ideal ICS and uses examples of existing agents to indicate the extent to which therapies reach these goals. Results: Improved therapeutic efficacy in an ICS may be offset by an increase in systemic effects. The ideal characteristics of an ICS include optimal clinical efficacy and no toxicity in combination with a convenient and easy-to-use inhaler device. To achieve this optimal profile, an ICS should have the following: a high affinity for and potency at the glucocorticoid receptor; prolonged retention in the lung; minimal or no oral bioavailability (ie, high first-pass inactivation); and rapid, complete systemic inactivation. The formulation and type of inhaler device are also important considerations: they should provide deposition in the lung in both large and small airways with no absorption effects outside the lung. ICSs should be evaluated for administration with several different delivery devices to ensure ease of use by patients of all ages with different asthma severities. An ICS that can be administered QD is also likely to improve patient adherence by simplifying the treatment regimen. Conclusion: An ideal ICS should have a large therapeutic margin, be used safely and effectively for long periods, be administered QD, be suitable for use in patients of all ages and asthma severities, and offer both control and prevention of asthma symptoms and exacerbations.

Safety of inhaled corticosteroids in children.

Inhaled corticosteroids (ICS) are now first-line therapy for persistent asthma in children. The major safety concerns of long-term ICS therapy for childhood asthma are potential effects on adrenal function, growth, and bone mass. Dosage, type of inhaler device, and individual drug characteristics influence systemic effects of ICS. Sensitive measures of basal adrenal function can show statistically significant changes during ICS therapy, but these do not accurately predict clinically meaningful adrenal axis suppression. Adrenal insufficiency is rare and confined to children receiving high doses of ICS. Dose-related inhibition of growth has been seen in some short- and intermediate-term studies, but long-term studies have found no detrimental effect on final height. ICS therapy has not been associated with significant changes in measurements of bone and bone biomarkers, but more studies of high doses and of therapy in adolescents are needed. Overall, although ICS are the most effective anti-inflammatory treatment available for asthma, high doses of ICS in children are still of concern. The risk of high doses is compounded in children with concomitant allergic conditions that require multiple forms of topical corticosteroids. Benefits of ICS clearly outweigh potential adverse effects and risks associated with poorly controlled asthma. Risk can be minimized by using the lowest effective ICS dose, limiting systemic availability of the drug through proper technique to minimize swallowed drug, and selection of agents with efficient first-path hepatic inactivation of swallowed drug. Adjuvant treatments can reduce the dose of ICS required for asthma control, allowing a reduction in overall systemic exposure for most children with mild-to-moderate persistent asthma. Therefore, these agents should be added to, but should not replace, ICS therapy.

An interactive algorithm for the assessment of cumulative cortisol suppression during inhaled corticosteroid therapy.

The objective of the study was to develop an algorithm based on a pharmacokinetic-pharmacodynamic (PK/PD) modeling approach to quantify and predict cumulative cortisol suppression (CCS) as a surrogate marker for the systemic activity of inhaled corticosteroid therapy. Two Excel spreadsheets, one for single dose and another for steady-state multiple doses of inhaled steroids, were developed for predicting CCS. Four of the commonly used inhaled steroids were chosen for the purposes of simulation: fluticasone propionate (FP), budesonide (BUD), flunisolide (FLU), and triamcinolone acetonide (TAA). Drug-specific PK and PD parameters were obtained from previous single- and multiple-dose studies. In cases in which multiple-dose data were not available, the single-dose data were extrapolated. The algorithm was designed to calculate CCS based on 5 input parameters: name of drug, dose, dosing interval, time(s) of dosing, and type of inhaler device. In addition, a generalized algorithm was set up to calculate CCS based on clearance, volume of distribution, absorption rate, protein binding, pulmonary deposition, oral bioavailability, and unbound EC50 of the corticosteroid of interest. The spreadsheet allowed predictions of CCS for single doses as well as steady-state conditions. A simple method has been developed that facilitates comparisons between various drugs and dosing regimens and has the potential to significantly reduce the number of comparative clinical trials to be performed for evaluating the short-term systemic activity of inhaled corticosteroids.

Generation of aerosolized drugs.

The expanding use of inhalation therapy has placed demands on current aerosol generation systems that are difficult to meet with current inhalers. The desire to deliver novel drug entities such as proteins and peptides, as well as complex formulations including liposomes and microspheres, requires delivery systems of improved efficiency that will target the lung in a reproducible manner. These efforts have also been spurred by the phase out of chlorofluorocarbons (CFCs) and this has included a directed search for alternative propellants. Consequently, a variety of new aerosol devices and methods of generating aerosols are being studied. This includes the use of freon replacement propellants, dry powder generation systems, aqueous unit spray systems and microprocessor controlled technologies. Each approach has advantages and disadvantages depending upon each principle of action and set of design variables. In addition, specific drugs may be better suited for one type of inhaler device vs. another. The extent to which aerosol generation systems achieve their goals is discussed together with a summary of selected papers presented at the recent International Congress of Aerosols in Medicine.