Association of prematurity, lung disease and body size with lung volume and ventilation inhomogeneity in unsedated neonates: a multicentre study

Abstract

Background: Previous studies have suggested that preterm birth with or without subsequent chronic lung disease is associated with reduced functional residual capacity (FRC) and increased ventilation inhomogeneity in the neonatal period. We aimed to establish whether such findings are associated with the degree of prematurity, neonatal respiratory illness and disproportionate somatic growth. Methods: Multiple breath washout measurements using an ultrasonic flowmeter were obtained from 219 infants on 306 test occasions during the first few months of life, at three neonatal units in the UK and Australia. Tests were performed during unsedated sleep in clinically stable infants (assigned to four exclusive diagnostic categories: term controls, preterm controls, respiratory distress syndrome and chronic lung disease). The determinants of neonatal lung function were assessed using multivariable, multilevel modelling. Results: After adjustment for age and body proportions, the factors gestation, intrauterine growth restriction and days of supplemental oxygen were all significantly associated with a reduced FRC. In contrast, increased ventilation inhomogeneity (elevated lung clearance index) was only significantly associated with duration of supplemental oxygen. After adjusting for continuous variables, diagnostic category made no further contribution to the models. Despite using identical techniques, unexpected inter-centre differences occurred, associated with the equipment used; these did not alter the negative association of preterm delivery and disease severity with lung function outcomes. Conclusion: Reduction in FRC is independently associated with prematurity, intrauterine growth restriction and severity of neonatal lung disease. Determinants of lung function shortly after birth are highly complex in different disease groups.Abnormal lung development in preterm infants caused by intrauterine and early postnatal factors 1 is characterised by impaired alveolarisation and dysmorphic vasculogenesis.2 These features are the pathological hallmarks of chronic lung disease of infancy (CLD, frequently referred to as bronchopulmonary dysplasia). Despite increasing survival of extremely preterm infants, the incidence of CLD remains high.3 While infants are generally categorised as having CLD or not based on the need for mechanical ventilation and/or supplemental oxygen (O 2 ) at 36 weeks postmenstrual age (PMA), the reality is that a continuum of disease severity is observed. [4][5][6][7] Accurate and non-invasive bedside techniques that evaluate the functional consequences of these structural changes are urgently required. Measurements of lung volume are relevant for assessing lung growth and development and for interpreting volume dependent lung function parameters. Functional residual capacity (FRC), the resting lung volume at end expiration, is the only ''static'' lung volume that can be readily assessed in non-cooperative infants and very young children. As summarised recently, 9 FRC is initially low in CLD but...

Growth of Lung Parenchyma in Infants and Toddlers with Chronic Lung Disease of Infancy

“…We found no significant difference between the CLDI and control groups for the nondimensional slopes over the region that alveolar gas concentration was estimated. This finding suggests marked ventilation inhomogeneity was not present in our CLDI group, which is consistent with data presented by Hü lskamp and colleagues, who reported a small effect on lung clearance index (LCI) with neonatal oxygen exposure; 100 days of oxygen exposure during the neonatal period correlated with an increase in LCI from approximately 7.0 to 7.3 (18). This small increase in LCI in infants with CLDI contrasts to a much higher LCI observed in clinically stable outpatient infants with cystic fibrosis (CF), who have an LCI of 8.4 (19).…”

Respiratory Muscle Activity Related to Flow and Lung Volume in Preterm Infants Compared With Term Infants

“…Some studies showed decreased endexpiratory volume [functional residual capacity (FRC)] and lung clearance index (LCI) (2) in sedated infants, whereas other studies in infants during natural sleep could not confirm these observed differences in FRC and LCI between healthy infants and infants with CLD (3). We (4) and other authors (3) indicated that the latter findings are in line with the following clinical observations: infants with CLD in natural sleep may have a high capacity to maintain relatively normal lung volume and relatively normal gas exchange, despite alterations to their lung mechanics, whereas this capacity may be reduced during sedation.…”

Nature and severity of lung function abnormalities in extremely pre-term children at 11 years of age

“…*: p,0.05; **: p,0.01; ***: p,0.0001. in persons with cystic fibrosis [30] it has not been found to be particularly discriminative when assessing BPD or prematurity either during infancy [31,35] or in the current study.…”