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

Abstract

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 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,CO2) and concentration (F_E,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,CO2 (ΔV_E,CO2) and the corresponding change of tidal volume (ΔV_T) was also analyzed. Nonlinear F_E,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,CO2 variability was attributed to the variability of V_T ( r² = 0.749), whereas in term and healthy preterm infants this relationship was weaker ( r² = 0.507 and 0.630, respectively). The ΔV_E,CO2 - ΔV_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.

Keywords: alveolarization; breathing variability; capnography; diffusional screening; lung dysmaturity.