Lung inflammation and simulated airway resistance in infants with cystic fibrosis

Abstract

Cystic fibrosis (CF) is characterized by small airway disease; but central airways may also be affected. We hypothesized that airway resistance estimated from computational fluid dynamic (CFD) methodology in infants with CF was higher than controls and that early airway inflammation in infants with CF is associated with airway resistance. Central airway models with a median of 51 bronchial outlets per model (interquartile range 46,56) were created from chest computed tomography scans of 18 infants with CF and 7 controls. Steady state airflow into the trachea was simulated to estimate central airway resistance in each model. Airway resistance was increased in the full airway models of infants with CF versus controls and in models trimmed to 33 bronchi. Airway resistance was associated with markers of inflammation in bronchoalveolar lavage fluid obtained approximately 8 months earlier but not with markers obtained at the same time. In conclusion, airway resistance estimated by CFD modeling is increased in infants with CF compared to controls and may be related to early airway inflammation.

Keywords: Airway mechanics; Computational fluid dynamics; Pediatrics.

Figure 1:

Airway Segmentation. (A) Airway segmentation overlaid on axial chest CT image. (B) Example of filled-in trachea (subtraction of endotracheal tube). (C) Airway centerline with tracheal and bronchial cross-sectional area measurements. Subset model (dark red) shows distal airways trimmed to 33 outlets.

Figure 2:

Computational Fluid dynamic model. (A) Detail showing distal airways trimmed cross-sectionally and the surface of the tetrahedral mesh. (B) Full airway geometry showing outlets clustered by lobe (indicated by color). Detail shows the tracheal plane with tetrahedral mesh. (C) Streamlines of inspiratory airflow estimated using computational fluid dynamics; red indicates faster velocities along streamlines, blue indicates slower velocities.

Figure 3:

Images of chest CT scans and airway segmentations from 4 CF infants and 4 control infants.

Figure 4:

Box plots of Resistance comparing the two groups (CF vs Control) using (A) Full airway models (Raw), (B) Trimmed models, and (C) Trimmed-and-scaled models.

Figure 5:

Correlation of % Neutrophils and Log Interleukin 8 (IL8) from epithelial lining fluid with Resistance (in CF Subjects only) at Visit 1 and Visit 2. Non-parallel slopes (A) indicate a significant study site interaction p-value (<0.15). Parallel slopes (B,C,D) indicate that the interaction p-value was not significant (>0.15).