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[State of the art of the inhalation therapy of asthma].

The current concept of asthma pathogenesis is that a characteristic chronic inflammatory process involving the airway wall causes the development of airflow limitation and increased responsiveness, thereby predisposing the airways to narrow in response to a variety of specific (allergic) or unspecific stimuli. Medications for asthma are used to reverse and prevent symptoms and airflow limitation and include controllers and relievers. The major advantage of delivering drugs directly into the airways via inhalation is that high concentrations can be delivered more effectively to the airways, and systemic side effects are avoided or minimized. Bronchodilators with or without anti-inflammatory substances are used as basic therapeutic approach in these patients. The stepwise approach to therapy recommends that the number/type and frequency of medications are increased with increasing asthma severity by adding systemic medications to existing inhalation therapy (step III-IV in asthma management guidelines). Combination therapy using a long acting beta 2-agonist and a glucocorticosteroid resulted in higher lung function improvement, and was superior in reduction of exacerbation rates compared with an inhaled glucocorticosteroid alone. Hence, the development of a fixed combination containing both substances in one device is a logic consequence, and thus, simplifying asthma therapy.

Administration, Inhalation↗

Inhalation therapy of the future--how will it change the way we treat asthma?

Inhalation of drugs has made a great difference in terms of optimizing asthma therapy. The challenge for the next generation of inhalers will be to provide still greater benefits to patients in terms of efficacy, safety, and convenience. Dry powder inhalers (DPIs) are innovative new inhalation devices and comparisons with pressurized metered dose inhalers (pMDIs) show that DPIs are at least as efficient at delivering drugs, and may be a superior delivery device for some drugs. To compare different inhaler devices, drug dose comparisons that lie on the slope of the dose-response curve should be selected, and it is important to analyze the risk:benefit ratio (therapeutic ratio). Some of the new devices contain aerosols with a smaller particle size than current designs. Monodispersed aerosols with a very narrow range of particle sizes may target drug delivery to specific areas of the lung where it is most effective. However, as smaller particles are more easily absorbed into the pulmonary circulation via the alveoli, these formulations may be associated with a higher incidence of systemic side effects. The optimal particle size required to maximize the therapeutic ratio of a molecule may be different for a beta2-agonist than for an inhaled corticosteroid. A greater understanding of this relationship will be required if we are to achieve better drug targeting with future inhalers.

Administration, Inhalation↗

Treatment of childhood asthma. Options and rationale for inhaled therapy.

Epidemiological studies suggest the prevalence of asthma is increasing, though some remain sceptical as to the magnitude or indeed the presence of an increase. However, despite improved diagnosis and the availability of the potent drugs now available there remains considerable respiratory morbidity associated with asthma. It is clear from a number of studies that failure to deliver drugs to the lungs when using inhaler devices is a factor contributing to this high level of morbidity. Failure of drug delivery may result from the prescribing of inappropriate devices, failure to use devices appropriately or failure to comply with a treatment regimen. For most of the currently available forms of asthma therapy there are significant advantages to be gained from administering them in aerosol form. The benefits to be derived from administering these drugs as an aerosol include a rapid onset of action for drugs such as beta-agonists and a low incidence of systemic effects from drugs such as beta-agonists and corticosteroids. Over the past 25 years our understanding of the nature of asthma has changed. Though this has been reflected in the emphasis on inhaled corticosteroid therapy in recent guidelines, it has not been reflected in the range of inhaler devices available. Manufacturers continue to place drugs such as corticosteroids in the same devices as short acting beta-agonists even though the requirements for these different drug classes are very different. It is likely that this contributes to suboptimal therapeutic responses with inhaled corticosteroids. However, the variability associated with current delivery systems is relatively small compared with the variability introduced by poor compliance. There is no work currently available to indicate how the use of cheap disposable devises which do not incorporate any form of positive feedback influence compliance with inhaled steroids. Optimising aerosolised drug delivery in childhood involves consideration of the class of drugs, the particular drug within a class but more importantly, the age and abilities of the child. Devices must be selected to suit a particular child's needs and abilities. Devices utilising tidal breathing are generally used such as spacing chambers or, less commonly these days, nebulisers. A screaming or struggling child, or failure to use a closely fitting mask, reduces drug delivery to the lungs enormously. Failure to respond to inhaled therapy in early childhood may be attributable to failure of drug delivery. Drug delivery in early childhood using current devices remains more an art than a science.

Administration, Inhalation↗

Efficacy and safety of inhalation therapy in chronic obstructive pulmonary disease and asthma.

The inhaled route has a number of well-recognized advantages over other routes for administration of drugs to the lungs. As the drug is delivered directly to its required site of action, only a small quantity is required for an adequate therapeutic response. Consequently, there is a low incidence of systemic side-effects compared with oral or intravenous administration. In addition, the onset of action of inhaled drugs is generally faster than that achieved by oral administration. Factors that can affect the quantity of inhaled particles reaching the lungs and their topographical distribution are manner of inhalation, aerosol characteristics and subject characteristics. The main types of inhaler device are metered-dose inhalers (MDIs), dry powder inhalers (DPIs) and nebulizers (jet and ultrasonic). There are advantages and disadvantages associated with all types of currently available inhaler device and there is still a clear need to develop more efficient devices that are easy to use. Respimat (Boehringer Ingelheim) is a novel soft mist inhaler that operates via a mechanism utilizing mechanical power rather than gas propellants, and represents an exciting development in this field.

Administration, Inhalation↗