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.

Are Asthmatics Enrolled in Randomized Trials Representative of Real-Life Outpatients?

“…In a cohort of patients aged ≥65 years, Soriano et al [32] reported an association between asthma and diseases of different organ systems (especially cardiac and respiratory). Moreover, in elderly patients, unintentional non-adherence to inhalation therapy represents a complex problem often related to comorbidities requiring multiple medications [33,34]. …”

Comparing Usability of NEXThaler®with Other Inhaled Corticosteroid/Long-Acting β2-Agonist Fixed Combination Dry Powder Inhalers in Asthma Patients

“…The full dose feedback system provides accurate dose metering and consistent full dose release independently of the inspiratory flow. (18,19) NEXThaler has a unique ''open-inhaleclose'' operating sequence that is at least one inhalation step less than that of other existing DPIs and easy for patients to use. Complex operating systems requiring several handling steps can increase the chance of making an error and lead to unintentional nonadherence of patients using their medication.…”

“…NEXThaler Ò (Chiesi Farmaceutici S.p.A.) is a DPI with an innovative full dose feedback system incorporating a novel breath-actuated mechanism (BAM): a click is heard and a dose counter decreases by one count, only after effective full dose delivery. (18,19) NEXThaler Ò provides a high lung deposition throughout the entire bronchial tree (56% of the emitted dose in patients with asthma), (19,20) and the BAM is activated at a consistent inhalation flow that is independent of disease severity and the level of asthma control, i.e., 35.0 and 35.4 L/min in patients with controlled and partially controlled/uncontrolled asthma, respectively. (21,22) At the time of writing this article (October 2013), NEXThaler is marketed in Germany, Spain, and The Netherlands, and has been approved in the following countries: Austria, Belgium, Bulgaria, Greece, France, Hungary, Italy, Luxembourg, Poland, Slovenia, and Slovakia.…”

Experimental and computational study of the effect of breath-actuated mechanism built in the NEXThaler® dry powder inhaler

“…It has also been demonstrated that Foster ® NEXThaler ® emits a high fraction of fine (diameter < 5 μm) and extrafine (diameter < 2 μm) particles (Buttini et al, 2016) with high lung deposition efficiency and a more uniform deposition distribution . The special internal design and structure of the inhaler is considered to contribute to the above characteristics of the drug (Scichilone et al, 2013). The most innovative feature of the device is the built in BAM (breath-actuated mechanism).…”