Tidal breath eNO measurements in a cohort of unsedated hospitalized neonates—A method validation

TY - JOUR

T1 - Tidal breath eNO measurements in a cohort of unsedated hospitalized neonates—A method validation

AU - J. Schmidt , Birgitte

AU - S. Reim , Pauline

AU - K., Jensen Andreas

AU - Albertsen, Per

AU - Greisen, Gorm

AU - M., Jørgensen Inger

N1 - doi: 10.1002/ppul.24019

PY - 2018/6

Y1 - 2018/6

N2 - Aim: Exhaled Nitric oxide (eNO) is an inflammatory marker. In 2002 Hall et al. [J Appl Physiol. 92:59-66] established an infant eNO measurement method, fulfilling four criteria of feasibility: simple, non-invasive, without impact on the natural breathing pattern, and accounting for flow by NO output (V'NO). Although tidal breathing is accepted as an eNO measurement method in uncooperative patients, it is seldom used outside research labs. The variability and lack of validated methods have restrained from exploring the area in preterm and term neonates the last years. This study aimed to validate clinically feasible longitudinal online tidal eNO and V'NO in a real-life birth cohort of un-sedated, hospitalized preterm, and term neonates. Method: We included 149 newborns, GA 28-42 weeks. Each scheduled for six repeated, non-invasive, on-line eNO measurements with Ecomedics CLD 88sp and NO-free air. We used three 60-second-eNO measurements. The method was adapted to fit preterm and term neonates with unstable respiration, without excluding sighs and surrounding breaths. Result: Protocol measurements with a maximum mutual difference of 1 ppb succeeded in 85-99%, increasing with postnatal age. We performed mixed model analyses in three hierarchical measurement levels. Despite the irregular breathing of newborns, the predictions of individual eNO levels in the average infant was a 0.05 SD. Exhaled NO was flow-dependent (P = 0.028); V'NO but not eNO was associated with preterm birth (P < 0.001) and >24 h CPAP treatment (P = 0.0316). Conclusion: We validated clinically, non-invasive, online eNO measurements in neonates. The method was well tolerated and exhibited low subject-specific-prediction-variance and high success rates.

AB - Aim: Exhaled Nitric oxide (eNO) is an inflammatory marker. In 2002 Hall et al. [J Appl Physiol. 92:59-66] established an infant eNO measurement method, fulfilling four criteria of feasibility: simple, non-invasive, without impact on the natural breathing pattern, and accounting for flow by NO output (V'NO). Although tidal breathing is accepted as an eNO measurement method in uncooperative patients, it is seldom used outside research labs. The variability and lack of validated methods have restrained from exploring the area in preterm and term neonates the last years. This study aimed to validate clinically feasible longitudinal online tidal eNO and V'NO in a real-life birth cohort of un-sedated, hospitalized preterm, and term neonates. Method: We included 149 newborns, GA 28-42 weeks. Each scheduled for six repeated, non-invasive, on-line eNO measurements with Ecomedics CLD 88sp and NO-free air. We used three 60-second-eNO measurements. The method was adapted to fit preterm and term neonates with unstable respiration, without excluding sighs and surrounding breaths. Result: Protocol measurements with a maximum mutual difference of 1 ppb succeeded in 85-99%, increasing with postnatal age. We performed mixed model analyses in three hierarchical measurement levels. Despite the irregular breathing of newborns, the predictions of individual eNO levels in the average infant was a 0.05 SD. Exhaled NO was flow-dependent (P = 0.028); V'NO but not eNO was associated with preterm birth (P < 0.001) and >24 h CPAP treatment (P = 0.0316). Conclusion: We validated clinically, non-invasive, online eNO measurements in neonates. The method was well tolerated and exhibited low subject-specific-prediction-variance and high success rates.

KW - biomarkers

KW - infant pulmonary function

KW - neonatal pulmonary medicine

KW - nitric oxide (NO)

KW - pulmonary function testing (PFT)

U2 - 10.1002/ppul.24019

DO - 10.1002/ppul.24019

M3 - Journal article

C2 - 29701312

SN - 8755-6863

VL - 53

SP - 762

EP - 771

JO - Pediatric Pulmonology

JF - Pediatric Pulmonology

IS - 6

ER -