Lung function deficits in children born very preterm versus at term
Children born very preterm had more airway obstruction, higher airway resistance, lower diffusion capacity and more ventilation inhomogeneity at 12 years of age than their term born controls. This was most evident before bronchodilator inhalation and was seen in a majority of the tests performed and both as absolute values and as percent of predicted normal values (Figure 1 and Tables 2 and 3).
Spirometry showed significantly more airway obstruction, measured as reductions in FEV1, FEV1/FVC and FEF25-75, in children born very preterm compared to term, both as absolute values and as percent of predicted (Figure 1A-C, Table 2). FEV1 below the lower limit of normal occurred in 23.5% of children born very preterm but only in 3.6% of children born at term (p=0.001). The corresponding proportions for FEV1/FVC were 25.0% versus 9.1% (p=0.014) and for FEF25-75 39.7% versus 10.9% (p<0.001). Dysanapsis ratio was lower in children born very preterm than in children born at term (p=0.004, Table 2).
Measurement of static lung volumes showed lower VC and higher RV as percent of predicted in very preterm infants, and also higher RV/TLC (Table 2 and 3). However, TLC and alveolar volume were not significantly different between children born preterm or at term.
Inspiratory, expiratory, and total airway resistance, as measured by body plethysmography, were higher in children born preterm (Table 3). Impulse oscillometry similarly showed a higher total resistance (R5, Figure 1D), frequency dependence of resistance (R5-R20) and resonant frequency (Fres), a lower reactance at 5 Hz (more negative X5), and an increased area under the reactance curve (AX; all p<0.001, Table 3), all indicating dysfunction of peripheral airways.
Diffusion capacity (DLCO) and the diffusion coefficient for CO (KCO) were significantly lower in preterm- than in term-born children (Table 3 and Figure 1E). However, the proportion of preterm-born children with measurements below the lower limit of normal was much smaller for DLCO (5.7% for children born preterm and 0% for term born controls, E-table 2) than for expiratory flows.
During N2 washout, children born very preterm had a significantly higher lung clearance index (both LCI2.5and LCI5.0) than children born at term (Table 3 and Figure 1F). This was most prominent for LCI2.5, indicating an increased ventilation inhomogeneity most evident in the peripheral airways.
Within the whole study population, children with FEV1/FVC or FEF25-75 below the lower limit of normal had significantly more often experienced wheezing, disturbed sleep or at least one of the symptoms listed in Table 1 (all p<0.05). A previous diagnosis of asthma was almost twice as common in children found to have FEF25-75 below the lower limit of normal than in those with a normal FEF25-75 (42.4% vs. 22.0%, p=0.004).