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Synonyms: chronic lung disease (CLD) of prematurity, BPD
In 1967 Northway et al first described the development of a new chronic lung disease in a group of premature infants who had respiratory distress syndrome (RDS) and received ventilation with high concentrations of oxygen.All these infants required oxygen at 28 days after birth and had progressive changes on CXR and classical pathological changes of necrotising bronchiolitis with alternating areas of alveolar over-inflation and atelectasis. This disease was termed as bronchopulmonary dysplasia (BPD) to emphasise that both airways and parenchyma of the lungs were affected.
BPD is a chronic lung disease that most commonly occurs in premature infants who have needed mechanical ventilation and oxygen therapy for infant RDS. However, it can also occur in immature infants who have had few signs of initial lung disease. Although the disorder is most often associated with premature birth, it can also occur in infants born at term who need aggressive ventilator therapy for severe, acute lung disease.
The clinical definition of BPD has evolved with time. The initial definition based on Northway's description defined BPD as presence of persistent respiratory signs and symptoms along with the need for supplemental oxygen, and an abnormal CXR at 28 days of age. The modern and the most widely used definition defines BPD as oxygen dependence at 36 weeks of postmenstrual age (gestational age plus chronological age). Most UK units use oxygen dependence at 36 weeks of postmenstrual age as the working definition for BPD.
The above-mentioned definitions do not indicate the level of oxygen dependence which can vary from needing low-flow oxygen to being ventilator-dependent. The assessment of severity is especially important in the research setting and to evaluate impact of any preventative or treatment strategies. To address this issue, the USA's National Institute of Health (NIH) has developed a consensus severity-based definition. This definition includes infants born at <32 weeks of gestation and needing more than 21% oxygen for at least 28 days.Assigning of severity requires a second assessment at 36 weeks of postmenstrual age in order to classify them as:
- Breathing room air at 36 weeks of postmenstrual age or discharge (whichever comes first) for babies born before 32 weeks; or
- Breathing room air by 56 days of postnatal age, or discharge (whichever comes first) for babies born after 32 weeks of gestation.
- Need for <30% oxygen at 36 weeks of postmenstrual age, or discharge (whichever comes first) for babies born before 32 weeks of gestation; or
- Need for <30% oxygen to 56 days pf postnatal age, or discharge (whichever comes first).
- Need for >30% oxygen, with or without positive pressure ventilation or continuous positive airway pressure (CPAP) at 36 weeks of postmenstrual age, or discharge (whichever comes first) for babies born before 32 weeks of gestation; or
- Need for >30% oxygen with or without positive pressure ventilation or CPAP at 56 days of postnatal age, or discharge (whichever comes first) for babies born after 32 weeks of gestation.
The NIH's recommended severity-based definition has been found to offer a better description of underlying lung disease and correlate well with infant maturity, growth and severity of illness.
A physiological definition of BPD has also been suggested in an attempt to overcome variation in practice and standardise the definition further. However, it is not widely used.
- BPD is a common complication of premature birth. The risk of developing BPD is inversely related to gestational age and birth weight.
- Infants are now described as having new BPD and may develop the condition despite having minimal or even no initial lung disease.
- Figures for incidence vary depending on criteria used. Using oxygen dependency at 28 days as the defining criteria, a UK study found that approximately half of all admissions, weighing <1250 g, to a UK neonatal intensive care unit, developed BPD.
- Population-based studies show rates of BPD among surviving infants still hospitalised at 36 weeks after birth range from 13-35%.
- In the most immature infants, even minimal exposure to oxygen and mechanical ventilation can be enough to contribute to BPD.
- The overall incidence of BPD is reported at about 20% of ventilated newborns, but wide variability exists between centres, probably because of regional differences in the clinical definitions of BPD, the proportion of newborns with extreme prematurity, and specific patient management.
- Numerous studies have explored the association between chorioamnionitis and BPD with conflicting results. A recent systematic review which pooled data from 59 studies concluded that the data show evidence of an association between BPD and chorioamnionitis. However, the authors found strong evidence of publication bias and concluded that despite a large body of evidence, chorioamnionitis cannot be definitively considered a risk factor for BPD.
Infants affected are usually immature and have very low birth weight.
- The most common clinical scenario is of a 23- to 26-weeks of gestation baby who over a period of 4-10 weeks progresses from needing ventilation to CPAP through to requiring supplemental oxygen.
- Most babies have initial RDS and require respiratory support in the form of ventilation or CPAP.
- They respond well to initial surfactant and ventilation, with improvement in the respiratory distress. However, in some there may be an increase in their oxygen and ventilatory requirements in the first two weeks of life.
- This dependence on respiratory support tends to continue and, although many will come off the ventilator or CPAP, the oxygen dependence continues.
- Many of these babies will continue to have tachypnoea, tachycardia and signs of respiratory distress, such as intercostal recession and nasal flaring.
- Infants with severe BPD have trouble feeding and gain weight poorly because of this and higher energy requirements.
- Bronchial hyperreactivity and wheezing can also occur.
- Some babies can develop pulmonary hypertension.
In an infant with a diagnosis of BPD, worsening of respiratory status can indicate presence of an additional condition such as:
- Pulmonary atelectasis.
- Air leak syndromes (include pulmonary interstitial emphysema, pneumomediastinum, pneumothorax, pneumopericardium, pneumoperitoneum and subcutaneous emphysema).
- Patent ductus arteriosus.
- Subglottic stenosis or tracheomalacia.
- Chest imaging is important in making the diagnosis and assessing for complications
- As the BPD evolves, the CXR changes with development of diffuse haziness and coarse interstitial pattern which reflects atelectasis, inflammation and/or pulmonary oedema. Areas of gas trapping may alternate with areas of atelectasis.
- In those with increase in respiratory distress or oxygen requirements, CXR helps to differentiate BRD from other conditions such as pneumonia or air leak syndrome.
- The diagnostic and prognostic usefulness of CXRs in BPD is highly variable.
- More recently, computerised tomography (CT) scanning has provided insights into the pathophysiology of BPD.CT and MRI scans can provide very detailed imaging of the lungs but are not routinely used.
- Arterial blood gases may show acidosis, hypercapnoea and relative hypoxia (for the inspired oxygen concentration).
- Continuous oxygen monitoring by using pulse oximetry is very useful to establish oxygen requirements and ensure appropriate oxygenation.
- Nasal CPAP is increasingly used at birth rather than ventilation even for the very preterm babies. A recent randomised controlled trial has shown that 50% of babies of 25-28 weeks of gestation can manage on CPAP without ever requiring intubation and ventilation. There is no increase in risk of death or BPD in this group and they are less likely to be oxygen-dependent at 28 days of age.
- If the baby does need intubation and ventilation it is important to minimise ventilation-associated lung injury. Strict monitoring and maintaining of tidal volumes along with use of synchronised ventilation modes is recommended.
- A Cochrane review has confirmed that early surfactant replacement therapy with extubation to nasal CPAP compared with later selective surfactant administration with continued ventilation is associated with less need for ventilation and lower incidence of BPD.
- High oxygen concentration can damage the lungs and eyes and it is recommended to maintain oxygen saturations at between 91-95%.
- Giving prophylactic steroids to mothers at risk of premature labour to reduce risk of infant RDS.
- Dexamethasone (corticosteroid) is effective in achieving short-term clinical improvement in ventilated babies as well as reducing the long-term risk of developing BPD. However, there is evidence that its use in the first week of life is associated with an increased risk of short-term adverse effects (gastrointestinal bleeding, intestinal perforation, hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth failure) and cerebral palsy.
- A Cochrane review of postnatal corticosteroid treatment initiated after 7 days of age suggests that late therapy may reduce neonatal mortality without significantly increasing the risk of adverse long-term neurodevelopmental outcome.However, it concludes that the current evidence is limited so the use of late corticosteroids should be reserved for babies who cannot be weaned off the ventilator.
- Furosemide and other diuretics such as chlorothiazide and spironolactone are used to treat fluid overload and are effective short-term therapy for ventilated babies. In preterm infants >3 weeks of age with BPD, acute and chronic administration of distal diuretics improves pulmonary mechanics.
- There is no evidence for efficacy of diuretics in non-ventilated babies so diuretics should be weaned and stopped once babies are stable off the ventilator.
- Aerosolised diuretics also have been investigated but have not demonstrated long-term benefit and are not recommended routinely.
- Studies have revealed that inhaled bronchodilators, most commonly beta-adrenergic agonists, can aid with short-term improvement in lung function and may be helpful to infants who have BPD during acute exacerbations.
- Methylxanthines such as caffeine are used to increase respiratory drive, decrease apnoea, and improve diaphragmatic contractility. During the international Caffeine for Apnea of Prematurity Trial which compared caffeine to placebo given within the first 10 days after birth, a significant reduction in BPD at 36 weeks of postmenstrual age was seen in the caffeine group (36% vs 47%).
- As yet there is no convincing evidence to support the use of the antioxidant superoxide dismutase.
- Inhaled nitric oxide relaxes the pulmonary vasculature and has been shown in some studies to improve long-term neurodevelopmental outcome. However, the results of a number of studies are mixed and the benefits of inhaled nitric oxide are unclear. Its routine use in neonates with respiratory failure is not recommended.
- Recent studies have not shown inhaled nitric oxide to be effective in preventing BPD.
- BPD is a complex condition so the best preventative strategy needs to target multiple aspects of this condition, including early diagnosis and treatment of antenatal and postnatal sepsis, optimal maintenance of oxygenation and fluid/electrolyte status, and aggressive early parenteral/enteral nutrition, along with appropriate ventilation strategies.
Sequelae and prognosis
- There is increased risk of poor neurodevelopmental outcome. Infants with birth weight of <1500g who have BPD have greater language delay as well as inreased fine and gross motor impairment.
- The first two years are the 'danger' period for airways disease. Affected infants can remain oxygen-dependent for many months and frequently require hospital re-admission in the first two years after birth.[2, 27]
- Chronic respiratory morbidity is a common adverse outcome in preterm infants with BPD. Recurrent respiratory symptoms requiring admission to hospital are common, particularly in those with respiratory syncytial virus (RSV)-associated lower respiratory tract infections (LRTIs). Although pulmonary function improves with age, air flow abnormalities may persist. The most severely affected may remain symptomatic and have evidence of airway obstruction even as adults.
- Infants with BPD are at an increased risk of developing serious pulmonary infection, particularly due to RSV. There is evidence that use of RSV monoclonal antibody injections (palivizumab) in the winter months reduces the risk of serious infection and hospitalisation. Recent study suggests that prophylaxis of RSV infection is cost-effective for the NHS.
- The Green Book recommends use of palivizumab prophylaxis in preterm infants with BPD during the RSV season.
- Vaccination against influenza should be considered.
Further reading and references
; Management of infants with chronic lung disease of prematurity in the United Kingdom. Early Hum Dev. 2005 Feb81(2):165-70. Epub 2005 Jan 16.
; Chronic lung disease after premature birth. N Engl J Med. 2008 Feb 14358(7):743-5
; Management and outcomes of very low birth weight. N Engl J Med. 2008 Apr 17358(16):1700-11.
; Premature baby, Premature Child
; Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med. 1967 Feb 16276(7):357-68.
; Long-term pulmonary outcome in the preterm infant. Neonatology. 200893(4):324-7. Epub 2008 Jun 5.
; Bronchopulmonary dysplasia. Lancet. 2006 Apr 29367(9520):1421-31.
; Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Jun163(7):1723-9.
; Is the new definition of bronchopulmonary dysplasia more useful? J Perinatol. 2005 Jan25(1):41-6.
; Impact of a physiologic definition on bronchopulmonary dysplasia rates. Pediatrics. 2004 Nov114(5):1305-11.
; Changing trends in the epidemiology and pathogenesis of neonatal chronic lung disease. J Pediatr. 1995 Apr126(4):605-10.
; Atypical chronic lung disease in preterm infants. J Perinat Med. 200432(2):162-7.
; Population-based study of bronchopulmonary dysplasia in very low birth weight infants in Switzerland. Eur J Pediatr. 2005 May164(5):292-7. Epub 2005 Feb 15.
; Chorioamnionitis as a risk factor for bronchopulmonary dysplasia: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2012 Jan97(1):F8-F17. doi: 10.1136/adc.2010.210187. Epub 2011 Jun 22.
; Reliability of CXR for the diagnosis of bronchopulmonary dysplasia. Pediatr Radiol. 2001 May31(5):339-42.
; What does imaging the chest tell us about bronchopulmonary dysplasia? Paediatr Respir Rev. 2010 Sep11(3):158-61. doi: 10.1016/j.prrv.2010.05.005. Epub 2010 Jun 2.
; Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med. 2008 Feb 14358(7):700-8. doi: 10.1056/NEJMoa072788.
; Early surfactant administration with brief ventilation vs. selective surfactant Cochrane Database Syst Rev. 2007 Oct 17(4):CD003063.
; Pitfalls, problems, and progress in bronchopulmonary dysplasia. Pediatrics. 2009 Jun123(6):1562-73. doi: 10.1542/peds.2008-1962.
; Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2010 Jan 20(1):CD001146. doi: 10.1002/14651858.CD001146.pub3.
; Late (> 7 days) postnatal corticosteroids for chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2014 May 135:CD001145. doi: 10.1002/14651858.CD001145.pub3.
; Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease. Cochrane Database Syst Rev. 2000(3):CD001817.
; Adjunctive pharmacotherapy in neonates with respiratory failure. Semin Fetal Neonatal Med. 2009 Feb14(1):49-55. doi: 10.1016/j.siny.2008.08.002. Epub 2008 Oct 11.
; Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18354(20):2112-21.
; Superoxide dismutase for preventing chronic lung disease in mechanically Cochrane Database Syst Rev. 2001(1):CD001968.
; Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide. N Engl J Med. 2005 Jul 7353(1):23-32.
; Inhaled nitric oxide in preterm infants: an individual-patient data meta-analysis of randomized trials. Pediatrics. 2011 Oct128(4):729-39. doi: 10.1542/peds.2010-2725. Epub 2011 Sep 19.
; Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature Lancet. 2010 Jul 31376(9738):346-54. Epub 2010 Jul 23.
; Developmental sequelae in preterm infants having a diagnosis of bronchopulmonary dysplasia: analysis using a severity-based classification system. Arch Pediatr Adolesc Med. 2007 Nov161(11):1082-7.
; Long-term respiratory consequences of premature birth at less than 32 weeks of gestation. Early Hum Dev. 2013 Oct89 Suppl 2:S25-7. doi: 10.1016/j.earlhumdev.2013.07.004. Epub 2013 Jul 30.
; Severe respiratory syncytial virus bronchiolitis: epidemiologic variations associated with the initiation of palivizumab in severely premature infants with bronchopulmonary dysplasia. Pediatr Infect Dis J. 2004 Dec23(12):1081-5.
; Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children: a UK analysis. Pharmacoeconomics. 200725(1):55-71.
; Public Health England (March 2013)
; Public Health England
Hi - my son had this condition and was operated on at 4 weeks. We were told at the time it is usually noticed at 3 months plus and he was very young and the muscle was very thick. He is now nearly 2...Guest
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