Dose-response Effects of Two Sizes of Monodisperse Isoproterenol in Mild Asthma

Abstract

The dose-response effect of monodispersed isoproterenol of two different sizes (diameters 2.5 and 5 microns) was examined in eight mild asthmatic subjects (baseline FEV, 81.5% of predicted). Pulmonary and cardiovascular variables were measured before and following 1, 2, 4, 8, and 16 cumulative min of aerosol inhalation. Subjects inhaled 1 to 30 micrograms (2.5-microns particles) or 2 to 50 micrograms (5-microns particles) of isoproterenol. Pulmonary but not cardiac responses were significantly greater for the 2.5-microns particles as compared to equivalent doses of 5-microns particles. Pulmonary dose-related response differences were particularly marked for variables associated with small airway function (FEF25-75 and FEF75-85). These findings suggest that small particles penetrate more deeply into the lung and thereby more effectively dilate small airways and that small amounts of appropriately sized inhaled bronchodilator may produce considerable therapeutic effects.

Avanços na inaloterapia em pediatria

“…[8][9][10][11][12] However, in patients with chronic obstructive pulmonary disease, the ideal size ranges from 2 to 3 µm. [13][14][15][16] The size and density of aerosol particles are classified according to a mass median aerodynamic diameter (MMAD). For uniform-sized spherical particles, MMAD is defined as the particle diameter multiplied by the square root of the particle density.…”

Anatomy and physiology in delivery: can we define our targets?

“…Particles above 5 pm in diameter are most likely to be deposited in the mouth and throat; thus, most of these are eventually swallowed. A study of eight patients with mild asthma who inhaled isoproterenol particles of 2.5 and 5 pm in diameter showed that the percentage increases (from baseline] in FEVl, SGaw and FEF25-75, and the decrease in FRC, were greater for the smallest particles ( 6 ) . These lung-function results also suggest a fairly even spread of drug throughout the airways for both formulations.…”

Lung Dose, Distribution, and Clinical Response to Therapeutic Aerosols

“…In general, those aerosols with mass medium aerodynamic diameter (MMAD) < 5 pm produce optimal response, whether the aerosol is inhaled from a MDI (Rees et al, 1982) or jet nebulizer (Johnson et al, 1989;Patel et al, 1990). However, it is evident from the studies shown in Table 6 that inhalation of equal drug doses generated as different sized aerosols, can produce equivalent responses despite differences in particle size and initial distribution of the aerosol within the lung (Dolovich et al, 1981a;Mitchell et al, 1987;Wollmer et al, 1987).…”