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

The concept of diffusional screening implies that breath-tobreath 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 postmenstrual 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,V-CO2) and concentration (F-E,F-CO2) were determined by volumetric capnography, whereas their variance was assessed by linear and nonlinear variability metrics. The relationship between relative breath-to-breath change of V-E,V-CO2 (Delta V-E,V-CO2) and the corresponding change of tidal volume (Delta V-T) was also analyzed. Nonlinear F-E,F-CO2 variability was lower in CLDI compared with term and non-CLDI preterm group (P < 0.001 for both comparisons). In CLDI infants, most of the V-E,V-CO2 variability was attributed to the variability of VT (r(2) = 0.749), whereas in term and healthy preterm infants this relationship was weaker (r(2) = 0.507 and 0.630, respectively). The Delta V-E,V-CO2 - Delta V-T slope was less steep in the CLDI group (1.06 +/- 0.07) compared with 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. NEW & NOTEWORTHY Young infants exhibit appreciable breath-to-breath CO2 variability that can be quantified by nonlinear variability metrics and may reflect the degree of lung dysmaturity. In infants with moderate/severe chronic lung disease of infancy (CLDI), the variability of the exhaled CO2 is mainly driven by the variability of breathing, whereas in term-born and healthy preterm infants this relationship is less strong. The slope of the relative CO2-to-volume change is less steep in CLDI infants, suggesting that dysmature lungs are less efficient in eliminating CO2 under tidal breathing conditions.