ECFS 2020 - Optimizing pharmaceutical care in cystic fibrosis

120    www.ecfs.eu OPTIMIZING PHARMACEUTICAL CARE IN CYSTIC FIBROSIS AEROSOL THERAPY FOR CF LUNG DISEASE: THE BASICS CHAPTER 7 being “respirable”. This means that these particles have a relatively high probability of bypassing the upper airways. However, particles with a MMAD of 2–5 μm have a lower probability of being transported to and deposited in the small airways than parti- cles of 1–2 μm ( Figure 1 ). Unfortunately, small particles carry little drug. In addi- tion to the geometric size of the particle, the particle density determines transport velocity and deposition probability. Spheres that have the same transport velocity exhibit the same aerodynamic behavior and have similar deposition patterns in the lung. This means that particles that are geomet- rically large and are porous (i.e. have a low density) can behave aerodynamically like particles that are geometrically small and are nonporous (i.e. have a high density). This effect of density on aerodynamic diam- eter has been utilized in the development of dry porous particles for DPI tobramycin formulations. Among the most important patient-related determinants of lung deposition and distri- bution within the airways is the diameter of the large airways [6]. Young children have smaller airways and higher inspiratory airflows relative to adults, and both these parameters facilitate central airway deposi- tion ( Figure 1 ) [7]. A second patient-related factor determining particle deposition is the quality of the inhalation maneuver. This quality depends on age, physical capability, disease severity, and the cognitive ability of the patient to perform specific inhalation maneuvers. It is well recognized that even well-trained and capable patients can vary their inhalation technique considerably from day to day [8, 9]. A high inspiratory flow rate trations in central airways but much lower concentrations in the small airways. Unfor- tunately, it is even more challenging to effi- ciently target the small airways in diseased areas of the lung. 2 Aerosol particles and deposition From infancy, we inhale thousands of liters of air per day containing all sorts of aerosol particles, including microorganisms and Aspergillus spores. Upper and lower airways are highly efficient at trapping aerosol particles and transporting these particles out of the lungs through mucocil- iary and cough clearance mechanisms. For efficient aerosol treatment of both central and small airways it is important to consider a number of factors that determine whether a sufficient fraction of the inhaled particles can bypass the upper airways to be deposited onto the walls of large and small airways in diseased lung areas. These factors can be divided into particle-related factors and patient-related factors [6]. The most important particle-related factors that determine their aerodynamic behavior are shape, size, and density. The size distri- bution of an aerosol is usually described as the mass median aerodynamic diam- eter (MMAD), which refers to the droplet diameter above and below which 50% of the mass of drug is contained. The second important parameter is the geometric standard deviation (GSD), which is a measure of the spread of an aerodynamic particle size distribution. Aerosol particles smaller than 5 μm are often described as