We searched the Cochrane Library and MEDLINE with the terms "bronchopulmonary dysplasia" or "chronic lung disease", and "prematurity" with no date restrictions and looked at English-language articles. We did not exclude commonly referenced or highly regarded older publications. We also identified relevant articles from the reference lists of articles pinpointed by this search strategy Several review articles or book chapters were included because they provide comprehensive overviews that
SeminarBronchopulmonary dysplasia
Section snippets
Defining BPD
An ideal definition of BPD would use simple clinical observations that grade the severity, are generalisable across various clinical settings, and are predictive of late pulmonary morbidity. Despite extensive studies of premature infants with chronic lung disease, the definition of BPD remains difficult. The traditional definition lacks specificity, and fails to account for important clinical distinctions related to extremes of prematurity, and wide variability in criteria for the use of
History and epidemiology
The epidemiology and incidence of BPD have changed greatly over the past 40 years. In the early 1960s, oxygen and mechanical ventilation were used for premature infants with acute respiratory failure due to apnoea and respiratory distress syndrome. As these therapies were applied more widely, there was a growing recognition of premature infants who developed chronic pulmonary symptoms, hypoxaemia, and chest radiographic abnormalities. Shephard and colleagues16 reported that 50% of premature
Pathogenesis
BPD has a multifactorial aetiology (panel). It was originally ascribed to oxygen toxicity1 because of increased production of cytotoxic oxygen free radicals, which can overwhelm the host antioxidant defence mechanisms, and cause lung inury.48, 49 Premature infants are deficient in antioxidant enzyme systems at birth, and have low levels of antioxidants such as vitamins C and E, increasing their vulnerability to oxygen toxicity. Ventilator-associated lung injury because of volutrauma could be
Respiratory function
Chronic respiratory signs in children with BPD include tachypnoea with shallow breathing, retractions, and paradoxical breathing pattern; coarse rhonchi, rales, and wheezes are typically heard on auscultation. The increased respiratory rate and shallow breathing increase dead space ventilation. Non-uniform damage to the airways and distal lungs results in variable time constants for different areas of the lungs, the inspired gas might be distributed to poorly perfused lungs, and worsening
Long-term outcome
Most follow-up data have been obtained from patients treated before surfactants were used. About half of all infants with BPD will need to be re-admitted to hospital during early childhood for respiratory distress, particularly if they develop respiratory syncytial virus infection.81 This high rate of hospitalisation generally falls during the second and third year of life,82 but lung function studies often show limited reserve even in patients with minimal overt respiratory signs.83, 84 This
Prevention
Factors that contribute to the pathogenesis of BPD are myriad. Thus, prevention needs a multidisciplinary approach. The use of antenatal steroids in mothers at high risk of delivering a premature infant reduces the incidence of neonatal death and respiratory distress syndrome by 50%,99 but even in combination with postnatal surfactant, fails to reduce the incidence of disease. Similarly, large randomised trials have not shown thyrotropin-releasing hormone to reduce BPD.100 Exogenous surfactant
Emerging preventive treatments
A promising method for preventing the development of BPD is prophylactic supplementation of human recombinant antioxidant enzymes.123 In preliminary studies in premature infants, the prophylactic use of both single and multiple intratracheal doses of recombinant human CuZn superoxide dismutase (rh superoxide dismutase) seemed to mitigate inflammatory changes and severe lung injury from oxygen and mechanical ventilation with no associated toxicity. In a randomised, placebo-controlled trial,
Conclusion
Nearly 40 years after its original description, BPD remains a major complication of premature birth and a challenge for the future. BPD has evolved to be characterised largely by inhibition of lung development. Future strategies that improve long-term outcomes will depend on the successful integration of basic research on fundamental mechanisms of lung development and the response to injury, as well as studies that test novel interventions to lower the occurrence and severity of the
Search strategy and selection criteria
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