Fig 1.
Coupled mouthpiece/upper/lower airway model.
Coupled mouthpiece/upper/lower airway model subdivided in multiple regions. Airways are segmented up to the 5th-9th generation.
Table 1.
Baseline characteristics.
Fig 2.
Comparison of CF-CT subscores per lobe.
Comparison of CF-CT subscores per lobe, presented as % of max CF-CT score. Data are presented as median (range), unless otherwise indicated. White bars represent bronchiectasis score, light grey bars represent airway wall thickening score and dark grey bars represent air trapping score. RUL = right upper lobe (n = 22), RML = right middle lobe (n = 22), RLL = right lower lobe (n = 40), LUL = left upper lobe (n = 39), LLL = left lower lobe (n = 39).
Fig 3.
Differences between lobes in AZLI concentrations.
Differences between lobes in AZLI concentrations for the scenario of thick airway surface liquid with largest aerosol diameter. Data are presented as median (range), unless otherwise indicated. Significant differences in AZLI concentrations were found between all lobes, except for one pairwise comparison (see S1 Table). RUL = right upper lobe, RML = right middle lobe. RLL = right lower lobe, LUL = left upper lobe, LLL = left lower lobe.
Table 2.
Inverse correlation between AZLI concentration in a lobe and the CF-CT scores.
Fig 4.
Percentage area of small airways with AZLI <10xMIC90.
Percentage area of small airways with AZLI concentrations <10xMIC90. Data are presented as median (range) for the different scenarios. White bars represent the smallest aerosol diameter (2.9 μm), light grey bars represent the median aerosol diameter (3.18 μm) and dark grey bars represent the largest aerosol diameter (4.35 μm). ASL = airway surface liquid.
Fig 5.
Relative AZLI concentrations in central and small airways of 2 patients for 3 different scenarios.
Simulations of AZLI deposition in 2 patients, representing 3 scenarios of varied airway surface liquid thickness (ASL) and aerosol diameter. Severity of CF lung disease was determined by the CF-CT score (% of total CF-CT score). Scenario a = thin ASL with smallest aerosol diameter; scenario b = median ASL with median aerosol diameter; scenario c = thick ASL with largest aerosol diameter. Part 1a, 1b and 1c: Patient 1, mild CF lung disease: bronchiectasis 0.0%, airway wall thickening 0.0% and air trapping 11.1%. Patient 1 received concentrations > 10xMIC90 in the central and small airways independent of ASL thickness and aerosol diameter (Part 1a, 1b, 1c). Part 2a, 2c and 2c: Patient 2, more severe lung disease: bronchiectasis 12.5%, airway wall thickening 11.1% and air trapping 38.9%. Patient 2 received concentrations > 10xMIC90 in the central and small airways in scenario a and b (Part 2a and 2b), but AZLI concentrations < 10xMIC90 in the small airways in scenario c (right upper and middle lobes) (Part 2c).
Fig 6.
Influence of inhalation technique on AZLI concentrations.
Influence of inhalation technique on AZLI concentrations presented as percentage area of small airways with AZLI <10xMIC90. Low breathing profile: tidal volume of 6 ml/kg (228 ml) and respiration rate of 14 breaths/min. Average breathing profile: tidal volume of 10 ml/kg (380 ml) and respiration rate of 18 breaths/min. High breathing profile: tidal volume of 14 ml/kg (532 ml) and respiration rate of 22 breaths/min. Data are presented as median (range) for the different scenarios. Light grey bars represent the scenario of median ASL (5 μm) with largest aerosol diameter (4.35 μm). The darker grey bars represent the scenario of thick ASL (7 μm) with median aerosol diameter (3.18 μm) and the darkest grey bars represent the scenario of thick ASL (7 μm) with largest aerosol diameter (4.35 μm). The scenarios of thin ASL with all diameters, median ASL with smallest and median diameter and thick ASL with smallest diameter are not represented as all breathing profiles resulted in AZLI concentrations above 10xMIC90. ASL = airway surface liquid.