The functional assessment of the response to bronchodilators in 2- to 5-year-old asthmatic children is technically difficult. For this reason, there have been no reports on the effects of long-acting bronchodilators, such as salmeterol, in this age group. Of the several techniques available for measuring resistance to airflow, forced oscillation remains the most adaptable to young children and the most practical for research and clinical use. In this stud we used the Jaeger MasterScreen Impulse Oscillometry System to assess the response of 2 to 5 year-old asthmatic children to an inhaled long-acting bronchodilator, salmeterol, by comparing it to the effect of a standard dose of the short-acting bronchodilator, albuterol. We performed a placebo-controlled, randomized, crossover study in 10 children aged 2 to 5 years who had a history of physician-diagnosed asthma and who were not on regular controller therapy. At weekly intervals after baseline measurements of reversibility, each child received two inhalations from an albuterol metered-dose inhaler (MDI) with a spacer (200 microg), or placebo MDI with spacer, or two inhalations from a salmeterol MDI (50 microg), or 50 microg from a salmeterol Diskus. Measurements were obtained at 5, 30, 60, 360, and 540 min, the last time interval only on the salmeterol days. Based on previous studies, total respiratory system reactance at 5 Hz (X5), calculated by the MasterScreen computer from mouth pressure and flow data, was used as the primary efficacy variable. The mean intra-individual variability in X5 was 10.5% (range 3.6% to 17.9%). The mean (SE) changes from baseline X5 at each time point were as follows: for placebo, 9.6 (3.0), 10.1 (2.6), 5.1 (2.9), 6.1 (3.5), p=0.36 vs. baseline; after treatment with albuterol, 32.7 (3.8), 53.9 (1.2), 47.3 (5.4), 18.1 (5.8), p<0.01 vs. baseline at all time points; after salmeterol MDI, 16 (6.4), 28.9 (5.2), 32.7 (3.9), 34.6 (4.4), 31.2 (4.8), p<0.05 at 60, 360, and 540 min; and after salmeterol Diskus, 16.4 (4.0), 16.9 (6.6), 27.8 (5.9), 28.6 (5.6), 33.8 (4.0), p<0.05 at 540 min. No significant adverse events or electrocardiographic changes were noted at any time. Impulse oscillometry is an acceptable method of assessing airway responses to bronchoactive drugs in this age group. Compared to albuterol and to its effect in older children and adults, the response to salmeterol Diskus appears to be somewhat blunted in this age group. The MasterScreen system is well suitedfor pharmacodynamic studies and clinical investigations in pre-school-aged children.

Central (large airway) and peripheral (small airway) dysfunction frequently occur in patients with asthma and chronic obstructive lung disease. Measurement of the respiratory impedance can assist with diagnosis of pathological conditions. The forced Oscillation technique (FOT) superimposes small pressure perturbations at the mouth during tidal breathing of a subject to measure lung mechanical parameters. The Impulse Oscillometry System (IOS) is a commercial instrument that measures forced oscillatory impedance. IOS can be conveniently used in children as it only requires their passive cooperation during pulmonary function testing. Forced oscillatory impedance can be analyzed with respiratory system equivalent electrical circuit models. Models of varying complexity and fidelity have been developed to provide better understanding of respiratory mechanics and enable greater specificity of the diagnosis. Parameter estimates for these models can be used as reference values for detection and diagnosis of different respiratory pathologies. Previous work by our group has evaluated several known respiratory models and a new RIC model (augmented RIC) has emerged which offers advantages over earlier models. It has been shown that one parameter of this new model (representing peripheral airway compliance) is capable of discriminating between normal and asthmatic children. In this paper, we analyzed IOS data from 40 Hispanic asthmatic children and obtained sensitive impulse oscillometric parameters of lung function as well as parameter estimates for the augmented RIC (aRIC) model to distinguish between constricted (asthmatic condition) and non-constricted (non-asthmatic condition) airways with very promising results.

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