Breath-to-breath variability of exhaled CO2 as a marker of lung dysmaturity in infancy

The concept of diffusional screening implies that breath-to-breath variations in CO₂ clearance, when related to the variability of breathing, may contain information on the quality and utilization of the available alveolar surface. We explored the validity of the above hypothesis in a cohort of young infants of comparable post-menstrual age but born at different stages of lung maturity, namely, in term-born infants (N = 128), preterm-born infants without chronic lung disease of infancy (CLDI) (N = 53) and preterm infants with moderate/severe CLDI (N = 87). Exhaled CO₂ volume (V_E,CO2) and concentration (F_E,CO2) were determined by volumetric capnography, while their variance was assessed by linear and non-linear variability metrics. The relationship between relative breath-to-breath change of V_E,CO2 (V_E,CO2) and the corresponding change of tidal volume (V_T), was also analyzed. Non-linear F_E,CO2 variability was lower in CLDI compared to term and non-CLDI preterm group (P<0.001 for both comparisons). In CLDI infants, most of the V_E,CO2 variability was attributed to the variability of V_T (R² 0.749), while in term and healthy preterm infants this relationship was weaker (R² 0.507 and 0.630, respectively). The _VE,CO2-VT slope was less steep in the CLDI group (1.06 ± 0.07) compared to non-CLDI preterm (1.16 ± 0.07; P <0.001) and term infants (1.20 ± 0.10; P <0.001), suggesting that the more dysmature the infant lung the less efficiently it eliminates CO₂ under tidal breathing conditions. We conclude that the temporal variation of CO₂ clearance may be related to the degree of lung dysmaturity in early infancy.

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