Regional Lung Deposition and Bronchodilator Response as a Function of β₂-Agonist Particle Size

Abstract

Regional targeting of inhaled beta2-agonist to the proximal airways is more important than distal alveolar deposition for bronchodilation. Altering intrapulmonary deposition through aerosol particle size can appreciably enhance inhaled drug therapy and may have implications for developing future inhaled treatments.

Inhaler technique and training in people with chronic obstructive pulmonary disease and asthma

“…The use of extra-fine particle pMDIs has been Review shown to demonstrate equivalent efficacy to other preparations but with a reduced equivalent dose of corticosteroid [25][26][27][28]. These newer formulations have been reported to be less dependent upon inhaler technique than other MDIs due to longer duration of aerosol emission [29] and lung deposition being affected less by inspiratory flow [30] and coordination [31].…”

“…This knowledge is useful since it is known that b 2 receptors predominate in the small conducting airways and alveoli; however, airway smooth muscle is present in the trachea and small conducting airways [30,38]. Consequently the ideal particle size for inhaled b 2 -agonists will be in the top end of the range of 1-5 µm, as this would allow deposition of drug particles in the region of airway where both airway smooth muscle and b 2 receptors exist.…”

“…Consequently the ideal particle size for inhaled b 2 -agonists will be in the top end of the range of 1-5 µm, as this would allow deposition of drug particles in the region of airway where both airway smooth muscle and b 2 receptors exist. Larger particles of b 2 -agonists in the range of 3-6µm have been demonstrated to achieve greater lung deposition in the central and intermediate airways than small particles (1.5 µm), and consequently produce greater bronchodilation [30]. By contrast, airway inflammation is present throughout the respiratory tract, although there is a similar, but more severe, inflammatory process in the peripheral airways compared with the central airways [45].Consequently, a particle size distribution from <1 µm up to 5 µm may be desirable for inhaled anti-inflammatory drugs, such as corticosteroids [38,46].…”

“…By contrast, airway inflammation is present throughout the respiratory tract, although there is a similar, but more severe, inflammatory process in the peripheral airways compared with the central airways [45].Consequently, a particle size distribution from <1 µm up to 5 µm may be desirable for inhaled anti-inflammatory drugs, such as corticosteroids [38,46]. Usmani et al described the lung deposition and clinical effects of three sizes (1.5, 3 and 6 µm) of monodisperse salbutamol in 12 asthmatic patients [30]. Although lung deposition was greatest for the 1.5 µm particles, the 6 µm particles produced the greatest clinical response in terms of lung function.…”

Targeting the small airways with dry powder adenosine: a challenging concept

“…[1–3] An advantage of small-particle instead of large-particle inhaled treatment could be a higher total lung deposition in addition to better deposition in the small airways. [4,5] Yet, we are currently not able to select asthma patients with small airway dysfunction, i.e.…”