IL MULTIPLE BREATH WASHOUT NELLA VALUTAZIONE DEL DANNO POLMONARE CRONICO NEI BAMBINI NATI CON GRANDE PREMATURITA’

Background. Survivors of very premature birth (<32 weeks of gestation) may have long-term respiratory impairment, especially in the presence of bronchopulmonary dysplasia (BPD). Multiple breath washout (MBW) derived indices (Lung Clearance Index -LCI-, Scond, Sacin) might be useful markers of chronic respiratory impairment in 1) children born <32 weeks of gestation with a history of intrauterine growth restriction (IUGR) and in 2) extremely preterm born children (<28 weeks). We evaluated whether these indices are more sensitive than more commonly used lung function tests (spirometry and TLco) to detect abnormal lung function in these groups of preterm children. Methods. In two different studies, spirometry, TLco and MBW (LCI, Sacin, Scond) were cross-sectionally evaluated in subjects aged 8.0-15-0 years who were born at <32 weeks of gestation with and without a prenatal diagnosis of IUGR or belonging to the cohort of children born at <28 weeks of gestation in Udine, between 2004 and 2010. A control group of children born ≥37 weeks of gestation was also included. Results. 1) Effects of IUGR on lung function in very preterm children Final study population included 28 very preterm children with IUGR, 67 without and 67 controls. Preterm children with IUGR had much higher prevalence of BPD (42% vs 10%) and significantly lower FEV1 z-score than those without IUGR (-0.51±0.94 vs 0.15±1.08; P = 0.006), whereas LCI and TLCO did not differ between the two groups. At simple regression, while BPD was significantly associated with either FEV1 z-score, TLco z-score and LCI, IUGR was negatively associated only with FEV1 z-score (B = -0.66; P = 0.004). At mediation analysis, 35% of the total effect of IUGR on FEV1 depended on BPD. 2) Effects of extremely preterm birth on lung function at school age. 47 extremely preterm born children and 60 controls were included in the final analysis. There were significant differences between children born <28 weeks of gestation and controls at term for FEV1 z-score, FVC z-score, TLco z-score, LCI and Scond, but not for Sacin. Among extremely preterm children, those with BPD (36%) had a much lower FEV1 z-score than those without BPD (-1.18 vs 0.02, P< 0.0001) but did not differ in the MBW indices. 29% of children born extremely preterm had abnormal Scond (>95% percentile of controls) but only 14% had abnormal FEV1 z-score (<5° percentile of the reference population). At multiple linear regression, current asthma had a positive association with Scond (B= 0.019, P = 0.04) and also increasing age had a small but significant effect (B=0.004, P = 0.004). Conclusion. IUGR affects larger airway function in survivors of very preterm birth at school age but not markers of more peripheral function, such as LCI and TLco. Among children born <28 weeks of gestation, Scond, reflecting ventilation inhomogeneity mainly arising within small airways, was the index more frequently abnormal in both children with and without BPD but the clinical meaning of this finding should be clarified through prospective studies.