Lung function measured with SPECT in infants and children with bronchopulmonary dysplasia : correlation with respiratory management and clinical grading

Chronic lung disease, bronchopulmonary dysplasia (BPD) is a common and severe complication among extremely preterm born infants and infants with lung hypoplasia. Clinical grading of BPD is performed at 36 weeks postmenstrual age (or 56 days of age in moderately preterm infants) based on the need for supplemental oxygen. Oxygen requirement is a poor predictor for lung function in childhood and at adult age. We aimed to evaluate a lung function measurement for infants and children with BPD to complement clinical grading, evaluate the impact of respiratory management and standardize follow-up. No functional imaging of the lung in neonatal patients has been reported earlier. Single photon emission computed tomography (SPECT) is a technique that gives a functional imaging at a regional level within the lung. Previously the technique has not been available to use in non-cooperating patients that are small in body size. Recent technical advances and the development of a system for inhalation by our research group opened up the possibility of applying SPECT in neonatal patients. Our aim was to see if three different groups of patients, extremely/very preterm born infants, children with BPD or infants with congenital diaphragmatic hernia and lung hypoplasia, had lung function impairment with ventilation perfusion abnormalities within the lung.

In paper I and IV we compare ventilation (V) perfusion (Q) matching with clinical severity grading, clinical characteristics and respiratory support during the first week of life (paper IV) and for the whole stay in the neonatal unit (paper I). V/Q abnormalities were correlated with BPD severity grade. Increasing days with mechanical ventilation (MV) were negatively correlated with lung function measured by SPECT. Higher values of carbon dioxide on the first day of life and during the first week were associated with better V/Q matching. High mean airway pressure (MAP) day 1 of life, a large decrease in MAP and early weaning of mechanical ventilation were also associated with better V/Q matching. High MAP and oxygen demand at day seven of life were associated with an increased severity grade of BPD. Additionally we found that one third of the patients graded as Mild or Moderate BPD had widespread V/Q abnormalities.

In paper II we studied patients with lung hypoplasia and congenital diaphragmatic hernia. In this group, V/Q abnormalities were also associated with increasing days with MV but also increasing days with extracorporeal membrane oxygenation and persistence of pulmonary hypertension. In a follow-up study of 10-year-old children with BPD born preterm (paper III), we found less V/Q abnormalities than in the preterm infants but lower values of lung volume with good V/Q matching than expected in lung healthy children at that age. SPECT can be used as a measurement of lung function and evaluation of treatment in neonatal patients, infants and children and as a compliment to clinical grading and for follow-up of lung function in survivors with BPD. Ventilation perfusion matching abnormalities are common among patients with BPD both in the newborn period and at school age.

List of scientific papers

I. Bronchopulmonary Dysplasia: Clinical Grading in Relation to Ventilation/Perfusion Mismatch Measured by Single Photon Emission Computed Tomography. Kjellberg M, Björkman B, Rohdin M, Sanchez-Crespo A, Jónsson B. Pediatric Pulmonology. 2013: 1206-1213.
https://doi.org/10.1002/ppul.22751

II. Postoperative regional distribution of pulmonary ventilation and perfusion in infants with congenital diaphragmatic hernia. Björkman K, Kjellberg M, Bergström S E, Jónsson B, Lindahl S, Radell P, Rohdin M, Sanchez-Crespo A. Journal of Pediatric Surgery. 2011:2047-2053.
https://doi.org/10.1016/j.jpedsurg.2011.06.042

III. Ten-year-old children with a history of bronchopulmonary dysplasia have regional abnormalities in ventilation perfusion matching. Kjellberg M, Sanchez-Crespo A, Jónsson B. [Accepted]
https://doi.org/10.1002/ppul.24273

IV. Respiratory Management the First Week of Life Affects BPD Grading and Ventilation Perfusion Matching at Term Age. Kjellberg M, Sanchez-Crespo A, Jónsson B. [Manuscript]