Abstract
Medical aerosols are key elements of current chronic obstructive pulmonary disease (COPD) therapy. Therapeutic effects are conditioned by the delivery of the right amount of medication to the right place within the airways, that is, to the drug receptors. Deposition of the inhaled drugs is sensitive to the breathing pattern of the patients which is also connected with the patient’s disease severity. The objective of this work was to measure the realistic inhalation profiles of mild, moderate, and severe COPD patients, simulate the deposition patterns of Symbicort® Turbuhaler® dry powder drug and compare them to similar patterns of healthy control subjects. For this purpose, a stochastic airway deposition model has been applied. Our results revealed that the amount of drug depositing within the lungs correlated with the degree of disease severity. While drug deposition fraction in the lungs of mild COPD patients compared with that of healthy subjects (28% versus 31%), lung deposition fraction characteristic of severe COPD patients was lower by a factor of almost two (about 17%). Deposition fraction of moderate COPD patients was in-between (23%). This implies that for the same inhaler dosage severe COPD patients receive a significantly lower lung dose, although, they would need more.
Highlights
Chronic obstructive pulmonary disease (COPD) is the denomination for a number of lung conditions that cause breathing difficulties
Medical aerosols emitted by pressurized metered dose inhalers or dry powder inhalers (DPI) are key elements of current chronic obstructive pulmonary disease (COPD) therapy
Since deposition of aerosols within the airways is highly influenced by the breathing parameters, the evolution of all these breathing parameters as a function of disease severity predicts that patients from different disease stage categories will have different airway deposition fractions and distributions
Summary
Chronic obstructive pulmonary disease (COPD) is the denomination for a number of lung conditions that cause breathing difficulties. COPD is one of the most frequent airway diseases and is expected to become the third leading cause of death worldwide by 2020 [1]. Medical aerosols emitted by pressurized metered dose inhalers (pMDI) or dry powder inhalers (DPI) are key elements of current COPD therapy. Inappropriate handling of the inhaler device may cause low pulmonary aerosol drug deposition and low therapeutic effects. Too forceful inhalation may lead to high throat deposition by impaction and a low dose of the drug deposited in the lungs. For reliable simulation of aerosol drug transport and deposition within the airways, computer models need to be validated against in vitro and in vivo experimental measurements and should use realistic inputs. It is worth noting that in addition to their high intersubject variability, breathing parameters are functions of disease severity
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