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Chronic respiratory sequelae are still a major health problem in surviving premature infants. These complications are less severe today than those originally described by Northway and collaborators in the 1960s,1 but occur more frequently now as the survival of extremely low birth weight infants has increased. The underlying alteration in lungs with bronchopulmonary dysplasia (BPD) is an arrest of alveolar and capillary development. The more severe cases are frequently associated with airway and vascular remodelling, leading to airway obstruction and pulmonary hypertension. These alterations, which may be accompanied by interstitial oedema and fibrous tissue proliferation, are responsible for the abnormalities in lung function observed in these infants.
The findings reported by Hjalmarson et al2 are in agreement with previous publications that have shown that extreme preterm infants frequently have abnormal lung function later in life, independent of their initial respiratory course compared with infants born at term.3 ,4 These abnormalities are characterised by lower specific lung compliance and lung volume, combined with airway obstruction that can lead to impaired gas distribution in the distal lung. These alterations are present in many preterm infants and are more striking in those who have more severe lung damage and are diagnosed as having BPD.
The term BPD was introduced by Northway et al1 to define a clinical, radiographic and pathological entity occurring in preterm infants with severe respiratory distress syndrome who survived after aggressive and prolonged mechanical respiratory support. Since then, different definitions of BPD have been proposed, most based primarily on the need for supplemental oxygen at a certain point in their clinical course. The need for supplemental oxygen is used as a surrogate for alteration in gas exchange and as an indicator of the severity of the lung damage. The duration and magnitude of the need for oxygen supplementation has been used to define the severity of the lung damage and to predict later respiratory outcomes. These definitions never implied that infants who do not meet specific diagnostic criteria have normal lungs but only intend to separate infants who have more severe lung disease from those who are less affected. The definitions were also introduced as a practical tool to compare outcomes between groups of infants exposed to different interventions in clinical trials or to compare outcomes between centres.
The need for oxygen supplementation is a crude marker of lung function that is subject to many factors that are not necessarily related to the severity of the lung damage.5 These include fluctuations in arterial oxygen due to alterations in central respiratory drive, the effects of different modalities of respiratory support, the use of different oxygenation targets, the use of medications such as steroids and caffeine, the influence of altitude and the effect of intercurrent respiratory illnesses.
The fact that an infant can maintain normal arterial oxygen levels while breathing room air at 36 weeks postmenstrual age does not mean that he/she has completely normal lungs nor does it rule out that alterations in lung structure or function may manifest later in life or when the infant is challenged. Using a specific age at which BPD is diagnosed is also arbitrary and rather simplistic. If one takes the most common BPD definition, oxygen requirement at 36 weeks postmenstrual age (PMA), an infant who is weaned to room air the day before reaching 36 weeks PMA would not be classified as having BPD, whereas one weaning to room air 1 day later would be diagnosed with BPD. This does not mean that the first infant will have normal lung function or that the second will be a pulmonary cripple. This problem was partly addressed by the formulation of the NIH definition of BPD where infants who receive more than 28 days of supplemental oxygen are classified as mild BPD even if they are breathing room air at 36 weeks.6 What seems to be clear is that the longer time an infant remains oxygen dependent the more likely is that he/she will have long-term pulmonary dysfunction.7 ,8
The fact that extremely premature infants frequently survive with altered lung function, irrespective of whether they meet diagnostic criteria for BPD or not, has been reported previously.3 ,4 It is clear that the lung damage associated with premature birth and the many factors that can interfere with lung development is not a simple presence or absence, but like most biological processes represents a continuum between normal lung growth and development and the striking alterations seen in the most severe forms of BPD.
Arterial oxygenation is only one crude measure of lung function, although an important one, that does not reflect the complex alterations in pulmonary function that can occur in these infants. It is very likely that a battery of tests measuring the different aspects of lung function including volumes, compliance, airway conductance, gas distribution and diffusion capacity would provide a more specific and sensitive tool to predict later lung health and function in these infants. However, most of these tests are complex and require sedation, expensive equipment and experienced individuals to perform and interpret. For these reasons, they are not practical for clinical or even research purposes.
Until more accurate and simpler tests to evaluate lung structure and function become available, neonatologists will continue to use basic indicators of gas exchange to classify these infants, keeping in mind the significant limitations of these simple markers to define populations at risk and to accurately predict lung function later in life.
Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.
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