High-resolution computed tomography imaging of airway disease in infants with cystic fibrosis

Abstract

Rationale: The development of early lung disease in patients with cystic fibrosis (CF) remains poorly defined.

Objective: Determine whether asymptomatic infants with CF have evidence for changes in airway structure when assessed by high-resolution computed tomography, and whether airway structure correlates with airway function in this age group.

Methods: Thirteen infants with CF (8-33 mo) and 13 control infants (7-25 mo) were evaluated. Airway wall and lumen areas were measured from three 1-mm-thick cross-sectional images obtained from upper, middle, and lower lobes during a respiratory pause with the lungs inflated to an airway pressure of 20 cm H2O. Lung tissue density was measured from images obtained during a respiratory pause at FRC. Forced expiratory flows were measured by the rapid thoracic compression technique in 11 infants with CF.

Results: Airway wall area increased more per unit increase in airway size, whereas airway lumen area increased less per unit increase in airway size in the CF than in the control group. Among infants with CF, a greater ratio of wall to lumen area correlated with lower airway function. In addition, lung density at relaxed (passive) FRC was lower for infants with CF than for control infants (0.38 vs. 0.43 g/ml; p < 0.02).

Conclusions: Our results indicate that infants with CF have thickened airway walls, narrowed airway lumens, and air trapping, when assessed by high-resolution computed tomography, and measurements of airway structure correlated with airway function.

Figure 1.

Total airway area (mm²) versus age (mo) for all of the individual airways measured from the individual control subjects (open squares) and subjects with cystic fibrosis (CF; solid circles). There was no significant difference in total airway area for the two groups (p > 0.85).

Figure 2.

Lumen area (mm²) versus total airway area (mm²) for all airways measured from control subjects (open squares) and subjects with CF (solid circles). The CF group had a less steep slope, which means that the lumen area increased less for the CF than for the control group with each unit increase in the total area. CF: lumen area = −0.197 + 0.133 × total area control; lumen area = −1.198 + 0.323 × total area.

Figure 3.

Wall area (mm²) versus total airway area (mm²) for all airways measured from control subjects (open squares) and subjects with CF (solid circles). The CF group had a steeper slope, which means that the wall area increased faster for the CF than control group with each unit increase in the total area. CF: wall area = 0.197 + 0.867 × total area control; wall area = 1.198 + 0.677 × total area.

Figure 4.

Wall area/total airway area versus airway size (mm²) for all airways measured from control subjects (open squares) and subjects with CF (solid circles). The CF group had a less negative slope, which means the ratio decreased less for CF than control group with each unit increase in the total area. CF: wall area to total area ratio = 0.914 − 0.003 × total area control; wall area to total area ratio = 0.960 − 0.013 × total area.

Figure 5.

Cumulative distributions of tissue densities measured from the high-resolution computed tomograpny images obtained from the lower lobes during respiratory pause at FRC. The subjects with CF (solid line) had significantly lower mean tissue densities than the control subjects (dashed line; p < 0.01).

Figure 6.

Comparison of lung tissue density (mean + SE) for control and CF groups. At FRC, infants with CF had significantly lower lung tissue density than control infants in the lower (p < 0.01) and middle lobes (p < 0.03), but not significantly different for the upper lobes (p > 0.55).

Figure 7.

For infants with CF, the ratio of wall area to lumen area versus FEV_0.5, expressed as z score. Greater airway wall thickening was associated with lower airway function (r² = 0.66, p < 0.002).