DELIVERY DEVICES FOR INHALED ASTHMA MEDICATION - CLINICAL IMPLICATIONS OF DIFFERENCES IN EFFECTIVENESS

This review deals with results of comparative clinical studies where 2 or more delivery devices have been used, the lung deposition of the d rug has been measured or is known and the clinical efficacy has been d ocumented. With optimal inhalation technique the lung deposition of in halation devices is approximately as follows: pressurised metered dose inhalers (pMDIs) 10 to 15% [salbutamol (albuterol) around 20%]; pMDI + spacer 20 to 30%; Rotahaler(R), Diskhaler(R) and Inhalator Ingelheim (R) around 10%; Easyhaler(R) 20 to 25%; and Turbuhaler(R) 20 to 35% of the metered dose depending on the substance. These differences in dep osition figures have been reflected in the results of most single-dose crossover studies with bronchodilator substances. A pMDI is clinicall y more effective than Rotahaler(R) and Diskhaler(R). Turbuhaler(R) is more effective than a pMDI. In single-dose studies where expected diff erences based on deposition values have been undetected, all responses have probably been on the top of the dose-response curves. Studies wi th a cumulative-dose design have not usually reflected known differenc es in deposition values between bronchodilator devices. This discrepan cy between single-dose crossover studies and cumulative-dose studies s eems to be the result of different doses and amounts of drug administe red at different time points (especially the first dose) in the cumula tive-dose studies. Studies with repeated doses over weeks and months d o not reflect differences in deposition values between bronchodilator devices, since short-acting bronchodilators, irrespective of the deliv ery system. do not affect the level of airway Function in the morning. There are only 2 studies comparing the efficacy of a long-acting bron chodilator given via 2 different devices. Anti-inflammatory medication is impossible to evaluate without using long screening periods, when the lowest required maintenance dosage of the inhaled corticosteroid h as to be individually defined. Comparative studies are meaningless wit hout knowing that patients are neither under- nor over-treated when en tering the study, Thereafter, comparisons can be made in studies with a duration of several months. Very few studies fulfil these criteria. However. the results of these types of studies do reflect differences in deposition values between delivery devices, Studies reported so far show that the budesonide Turbuhaler(R) is clinically approximately tw ice as effective as a budesonide pMDI or a beclomethasone pMDI with sp acer. The results of short-term studies seem to indicate that fluticas one is twice as effective as beclomethasone, irrespective of pMDI or D iskhaler(R) delivery system. So far no well-designed double-blind stud ies have been performed comparing the budesonide Turbuhaler(R) with fl uticasone via pMDI or Diskhaler(R). No deposition data are available f or fluticasone (in pMDI, Diskhaler(R) or Diskus(R)/Accuhaler(R)), or f or the most recent device introductions such as the Diskus(R)/Accuhale r(R) with any substance. The Easyhaler(R) (available with salbutamol o r beclomethasone) has good deposition values, but has not been compare d clinically with Turbuhaler(R), Diskhaler(R) or Diskus(R)/Accuhaler(R ). Even when used properly, delivery devices may deposit very differen t amounts of drug into the lungs. Also, pMDIs may have different depos ition properties. Recent studies with bronchodilators and corticostero ids have shown that there is a good correlation between the amount of drug deposited in the lungs and the level of clinical efficacy.