Tidal breathing parameters in extremely premature infants. Feasibility and clinical utility of electromagnetic inductance plethysmography

Abstract

Background: Extremely preterm (EP) birth is associated with adverse lung growth, due to disturbance of programmed and fine-tuned sequences of normal intrauterine development, as well as the trauma inflicted by life-saving treatments. Moreover, EP-born neonates are probably born with variable susceptibilities or predispositions for lung injury. The pulmonary consequences of EP birth are heterogeneous and insufficiently mapped and understood. Particularly, our understanding of the detailed lung mechanics in EP-born infants is limited, largely due to the fact that lung function measurements in neonates and infants are complex and not readily available. Electromagnetic inductance plethysmography (EIP) is a novel non-invasive system that provides tidal breathing parameters in the form of tidal flow volume loops.

With these studies, we aimed to: (1) Study feasibility and validity of the EIP method in preterm and term-born infants, (2) use the EIP method to compare lung function in EP and term-born infants at term-equivalent age, and test if lung function measurements obtained at this stage in EP-born infants were associated with respiratory health during their first year of life, and (3) study if tidal breathing parameters, obtained from a mechanical ventilator during the few first hours of life in EP-born neonates, could predict bronchopulmonary dysplasia (BPD).

Methods: In study #1, we tested repeatability of the EIP method in a total of 30 preterm born infants who were at various stages of their development. A nurse experienced with the system measured all patients before and after meals, and these measurements were repeated by nurses new to the system. In study #2, the EIP-method was validated against a ‘gold standard method’ (mask-based ultrasonic flowmeter) in 30 infants at postmenstrual ages between 36 to 43 weeks and weights from 2.3 to 4.8 kg, applying both methods simultaneously. In study #3, within a population-based design, 52 EP-born infants recruited at Haukeland and Stavanger University Hospitals had their lung function measured at term-equivalent age using the EIP method, and the results were compared with 45 term-born controls. The EP-born infants were followed during their first year of life, including clinical examinations and questionnaires addressing respiratory symptoms and treatments. In study #4, using custom made software, we calculated tidal breathing parameters from the flow signals of 33 ventilator treated EP born neonates during their first hours of life, and the data were compared between those who later developed moderate/severe versus no/mild BPD.

Results: We found in studies #1 and #2 that the EIP method was well tolerated by the infants and also feasible in a busy NICU setting. The repeatability was better for term-born than preterm-born infants, but comparable to what has been reported for “maskbased” infant spirometry. The experience of the personnel and the relationship to meals influenced the reproducibility. Tidal breathing parameters obtained by the EIP method corresponded well with those obtained by the “mask-based” system when applied simultaneously in infants at term-equivalent age. In study #3, we found that lung function measured by EIP was strikingly abnormal in EP compared to healthy term-born infants at term-equivalent age, characterized by obstructive pulmonary abnormalities, and by increased tidal volumes and minute ventilation. Abnormalities were most pronounced for the group of infants with BPD, but significantly present also in infants without BPD. The tidal breathing parameter TEF50/PTEF predicted respiratory morbidity in the first year of life in infants born EP. In study #4, we found that flow data easily obtained from a ventilator during the first 48 hours of life could be used to compute breathing parameters that discriminated between neonates who went on to develop the severe forms of BPD and those who did not.

Conclusions and implications: EIP emerges as a feasible method of infant lung function testing. Its major strengths are the relative simplicity by which it can be put to use, and the avoidance of a facemask. This thesis has demonstrated that EIP can provide tidal breathing measurements that can aid the characterization of lung disease after EP birth, and that tidal breathing parameters obtained shortly after birth may identify neonates with predisposition for a difficult clinical respiratory course. If subsequent evaluations were to confirm the findings of this thesis, EIP and tidal breathing parameters have the potential of early recognition of neonates at risk of the severe forms of lung disease of prematurity and of later respiratory morbidity, which may pave the way for lifelong targeted surveillance and guidance of clinical management and intervention studies.