Lung penetration and patient adherence considerations in the management of asthma: role of extra-fine formulations

Abstract

The mainstay of management in asthma is inhalation therapy at the target site, with direct delivery of the aerosolized drug into the airways to treat inflammation and relieve obstruction. Abundant evidence is available to support the concept that inflammatory and functional changes at the level of the most peripheral airways strongly contribute to the complexity and heterogeneous manifestations of asthma. It is now largely accepted that there is a wide range of clinical phenotypes of the disease, characterized primarily by small airways involvement. Thus, an appropriate diagnostic algorithm cannot exclude biological and functional assessment of the peripheral airways. Similarly, achievement of optimal control of the disease and appropriate management of specific phenotypes of asthma should be based on drugs (and delivery options) able to distribute uniformly along the bronchial tree and to reach the most peripheral airways. Products developed with the Modulite(®) technology platform have been demonstrated to meet these aims. Recent real-life studies have shown clearly that extra-fine fixed-combination inhaled therapy provides better asthma control than non-extra-fine formulations, thus translating the activity of the drugs into greater effectiveness in clinical practice. We suggest that in patients with incomplete asthma control despite good lung function, involvement of the peripheral airways should always be suspected. When this is the case, treatments targeting both the large and small airways should be used to improve asthma control. Above all, it is emphasized that patient adherence with prescribed medications can contribute to clinical success, and clinicians should always be aware of the role played by patients themselves in determining the success or failure of treatment.

Keywords: asthma; device; inflammation; quality of life; small airways.

Figure 1

Algorithm showing the switch from chlorofluorocarbon (CFC) to hydrofluoroalkane (HFA) propellants and development of extra-fine formulations.

Figure 2

Description of the Modulite^® technology (see text for details).

Figure 3

Changes in closing capacity measured by the single-breath nitrogen washout test in the two study groups. Note: The improvement is greater in the extra-fine beclomethasone-formoterol combination group than in the non-extra-fine fluticasone propionate-formoterol group. Abbreviations: CC/TLC, closing capacity/total lung capacity; FP/S, fluticasone propionate/salmeterol; BDP/F, beclomethasone dipropionate/formoterol.

Figure 4

Mass median aerodynamic diameter of inhaled corticosteroids + long-acting β2-agonist combinations. Abbreviations: BDP/F, beclomethasone dipropionate-formoterol; BUD/F, budesonide-formoterol; FP/S, fluticasone propionate-salmeterol; FP/F, fluticasone propionate-formoterol; pMDI, pressurized metered-dose inhaler; TH, Turbuhaler^®; MMAD, mass median aerodynamic diameter; LABA, long-acting beta2 agonist.

Figure 5

Scintigraphic image in a patient with asthma after inhalation of extra-fine beclomethasone dipropionate-formoterol 400/24 μg through the NEXThaler™ dry powder inhaler.