Broncho pulmonary dysplasia (BPD), which recently and more appropriately has been renamed as Chronic Lung Disease (CLD), results from the effects of positive pressure ventilation on a structurally and functionally immature lung. It is characterized primarily by prolonged need for ventilatory support, O2 requirements, need for home oxygen and readmission with respiratory illness in the first year of life. There is controversy over it’s most appropriate definition, preventive strategies and treatment modalities. The two most commonly used definitions are: <list list-type="bullet"><list-item>Oxygen requirements beyond 28 days of life with abnormal X-ray (<xref ref-type="bibr" rid="bib001">1</xref>), or</list-item><list-item>Oxygen requirements beyond 36 weeks post conceptional age (<xref ref-type="bibr" rid="bib002">2</xref>).</list-item></list>It has been argued that oxygen dependency beyond 36 weeks PCA is a more useful definition, as this rather than oxygen dependence at 28 days correlates more closely with continuing respiratory morbidity after discharge (<xref ref-type="bibr" rid="bib002">2</xref>).</sec><sec id="sec001"><title>Iincidence & risk factors

JNNFI

Journal of Neonatology

0973-21870973-2179

National Neonatology Forum

jn-17-4-004

Recent advances in the management of broncho - pulmonary dysplasia (BPD)

Chellani

Harish

Chopra

Manish

Neonatal Division, Department of Pediatrics, VMMC & Safdarjang Hospital, New Delhi 110029

10–122003

1742934

Broncho pulmonary dysplasia (BPD), which recently and more appropriately has been renamed as Chronic Lung Disease (CLD), results from the effects of positive pressure ventilation on a structurally and functionally immature lung. It is characterized primarily by prolonged need for ventilatory support, O2 requirements, need for home oxygen and readmission with respiratory illness in the first year of life. There is controversy over it’s most appropriate definition, preventive strategies and treatment modalities. The two most commonly used definitions are: <list list-type="bullet"><list-item>Oxygen requirements beyond 28 days of life with abnormal X-ray (<xref ref-type="bibr" rid="bib001">1</xref>), or</list-item><list-item>Oxygen requirements beyond 36 weeks post conceptional age (<xref ref-type="bibr" rid="bib002">2</xref>).</list-item></list>It has been argued that oxygen dependency beyond 36 weeks PCA is a more useful definition, as this rather than oxygen dependence at 28 days correlates more closely with continuing respiratory morbidity after discharge (<xref ref-type="bibr" rid="bib002">2</xref>).</sec><sec id="sec001"><title>Iincidence & risk factors

Over the last two decades, the incidence of BPD in VLBW neonates has increased from approximately 10% to 30%, most of the extra cases being explained by improved survival (3). However, data from our country is scanty. Generally CLD occurs in two circumstances (with overlap):

Infants who require ventilation via an endotracheal tube because of RDS or other disorders (particularly when high ventilator pressures and high FiO2 are required) may have a prolonged recovery period with persisting oxygen requirements and coarse reticular changes on chest X-ray.

An infant is considered to be predisposed to develop BPD, if he/she is born at <32 weeks of completed gestation, having RDS or any other severe lung disease, PDA/fluid overload and pulmonary interstitial emphysema (PIE). Major mechanisms of pulmonary injury proposed include infection and inflammation, baro-or, volu-trauma and oxygen toxicity (4).

Issues of concern in infants with BPD

A. Pulmonary Consequences (5)

The pulmonary function status of infants with BPD is characterized by low lung compliance, increased pulmonary resistance and increased energy used for breathing. This may result in:

Persistent oxygen and ventilation requirements.

Longer stay in hospital

Need for home oxygen

Use of additional therapies: post natal steroids and diuretics

Pulmonary hypertension if adequate oxygenation is not maintained (with subsequent cor-pulmonale and death)

Exacerbations due to respiratory infections in first year of life, especially with RSV resulting in increased incidence of re-hospitalization.

Increased incidence of bronchial hyper - reactivity (5)

Minimal functional abnormalities at long term follow up (6)

B. Neuro-developmental sequelae

Since 1990, several published studies of premature infants have examined the association between BPD and neuro-development as compared to infants without BPD. It was observed that in general, infants with BPD have significantly worse developmental outcomes including poorer cognitive outcomes, more developmental delays and higher rates of learning disabilities even after adjustment for confounding (7–11).

C. Physical growth

increased incidence of growth failure (weight and stature) as a consequence of increased energy expenditure, abnormal sucking patterns and iatrogenic limitation of fluids (5).

Management of BPD

Before discussing the treatment of established cases of BPD, we need to address to certain preventive strategies which although are of limited proven value at present may be helpful in preventing or decreasing the incidence of BPD.

I. Preventive Strategies

Early selective surfactant administration given to infants with RDS requiring assisted ventilation leads to a decreased risk of penumothorax, pulmonary interstitial emphysema and a decreased risk of neonatal mortality and BPD compared to delaying treatment of such infants until they develop established RDS (12).

Target appropriate oxygen levels in preterm infants. In the ‘STOP-ROP’ trial (13) use of supplemental oxygen at pulse oximetry saturations of 96-99% increased the risk of adverse pulmonary events including pneumonia and/or exacerbations of BPD and the need for oxygen, diuretics and hospitalization at 3 months of corrected age.

The BOOST trial (14) found no difference in growth or development from targeting saturations between 95–98% compared to 91–94%, but the higher saturation target group had a statistically significant longer duration of oxygen requirements, increased rates of BPD diagnosis and home oxygen.

Target FiO2 to obtain Pao2 60–80 mm Hg or

Saturations 90–95% in preterm infants

With conventional ventilation, target normal PaCo2 levels (40–60 mm Hg). Avoid overventilation of the lung resulting in hypocarbia (15) by using appropriate peak inspiratory pressure and inspiratory times to achieve tidal volumes of 3–4 mls/kg/min.

Prophylactic jet ventilation-There is a benefit in pulmonary outcomes in the group electively ventilated with HFJV. Of concern, however, is the significant increase in acute brain injury. There are as yet no long term pulmonary or neuro-developmental outcomes from any of the trials. Until further studies ascertain the most appropriate strategy to routinely ventilate premature infants with HFJV safely, ventilation with HFJV cannot be recommended for preterm infants with RDS (16).

Vitamin-A - Meta analysis suggests vitamin A supplementation results in reduced oxygen requirements at 36 weeks post menstrual age (17). Vitamin A 5000 U EVI, 3 times weekly for the first 28 days of age reduced the incidence of BPD in ELBW infants by 10%.

In < 28 weeks infants, intratracheal recombinant human Cu/Zu super-oxide dismutase administered intratracheally every 48 hours while intubated resulted in an approximately 50% reduction in use of asthma medications, emergency room visits and hospitalizations in the first year of life. This treatment remains investigational (18).

Use of antenatal steroids - although they are known to reduce mortality and the incidence of RDS in premature infants, they have not been found to alter the rate of development of BPD (19).

Avoid excessive fluid intakes in preterm infants (20), (21). It has been shown that infants who reviewed lOmls/Kg volume expansions on day 1 and 2 of life are more likely to develop BPD later on.

II. Treatment of established cases of BPD

A. In patient treatment

The goals of treatment during the NICU stay are to minimize further lung injury (baro and volutrauma, oxygen toxicity, inflammation), maximize nutrition and diminish oxygen consumption.

Mechanical ventilation in acute phase

Ventilator adjustments are made to minimize airway pressures while providing adequate gas exchange. Target to achieve PaCO2 between 40–60 mm Hg, PaO2 of 60–80 mm Hg; SaO2 90–95% and ph>7.25 (15).

Supplemental oxygen

(13, 14) should be given after weaning from the ventilator to ensure 90–95% saturation on a continuous pulse oximeter recording.

Postnatal steroids have been the mainstay of treatment. Timing of steroids has been as issue. They can be used as

Early postnatal steroids (< 96 hours)

Intermediate postnatal steroids (7–;14 days)

Late postnatal steroids (>3 weeks).

Early steroids (<96 hours) given to all ventilated infants result in many infants receiving steroids unnecessarily and are associated with high rates of intestinal perforation. Intermediate steroids (day 7–14) are given to infants at risk of BPD, are used to facilitate weaning from the ventilator and have been shown to be effective at reducing oxygen dependency at 36 weeks PCA. However, recent long-term follow up studies have created concerns regarding the long-term neuro-developmental effects of postnatal corticosteroids 22-25.

A systematic review (26) of 10 randomized controlled trials of postnatal steroids concludes that evidence exists to offer therapeutic postnatal corticosteroids to ventilated preterm infants at high risk of BPD, and that existing data are reassuring concerning long term outcomes of steroids used in a therapeutic manner. However, in view of the limited number of infants enrolled in the existing trials, more research is needed. Therefore, postnatal corticosteroids should only be offered after informed parental consent.

Indications for steroids-Consider if

failure to wean from ventilator, or

preterm infants with persisting oxygen and ventilation requirements >7 days of age.

Exclude other possible causes of respiratory deterioration including-

Infection

PDA, or

ET tube obstruction

Agent used is dexamethasone

Lower dose regimen

– 0.15 mg/kg/day 12 hourly for 72 hrs.

– 0.l0 mg/kg/day 12 hourly for 72 hrs.

– 0.05 me/kg/day 12 hourly for 48 hrs.

– 0.02 mg/kg/day 12 hourly for 48 hrs.

Consider repeating course or using a higher dose if there is no response.

– 0.5 mg/kg/day in 2 divided doses for 3 days.

– 0.3 mg/kg/day in 2 divided doses for 3 days.

– 0.2 mg/kg/day in 2 divided doses for 2 days.

– 0.1 mg/kg/day in 2 divided doses for 2 days.

– 0.05 mg/kg/day in 1 dose for 4 days.

Some babies may need a longer course if they deteriorate as the dose in being weaned down.

Side effects

Hypertension (9%), hyperglycaemia (44%); gastrointestinal perforation or bleeding (8%), myocardial hypertrophy (23%), infection and adrenal suppression.

Nebulised Steroids

There is no evidence till date that early administration (in the first 2 weeks of life) of inhaled steroids to ventilated preterm neonates is effective in reducing the incidence of BPD.

However, it may decrease the need for systemic steroids. Further studies are required before use of inhaled steroids can be recommended for the purpose.

VI. Fluids (20, 21)

In babies with BPD, lung function can be improved by avoiding fluid overload. Target to maintain urine output of at least 1ml/kg/hr and serum sodium concentration of 140–145 meq/L. Fluid intakes of up to 150ml/kg/dayare well tolerated by most babies

B. Long term management of BPD

Oxygen

After the acute period, adequate oxygen (home oxygen) needs to be provided for as long as necessary to achieve an oxygen saturation of 90–95%. Targeting higher doses may exacerbate lung disease (13), (14) and doesn’t help in long term growth or development.

Fluids & Nutrition

Infants with BPD have increased metabolic demands and in the acute stages, the energy requirements can be 20–40 percent greater than those of age matched controls and this necessitates an increase in the recommended caloric intake to about 150 kcal/kg/day (28) as compared to 110–120 kcal/kg/day of energy for the control preterms (29). Provide more calories to optimize growth by early administration of more lipids instead of carbohydrates. Besides, ensure adequate supplementation of feeds with vitamin A and E, selenium, zinc and copper as all these are vital to antioxidant enzymes functioning.

Diuretics

In preterm infants <3 weeks of age developing BPD, furosemide administration has either inconsistent effects or no detectable effect (30).

In infants > 3 weeks of age with BPD, a single intravenous dose of Img/kg of furosemide improves lung compliance and airway resistance for 1 hour. However, no long-term benefits have been shown thus, intermittent doses of furosemide are given if respiratory deterioration occurs or signs of fluid retention appear.

The administration of furosemide results in diuresis that minimizes total lung water and raises plasma oncotic pressure. However, furosemide also has important non-renal effects on pulmonary function which are evident soon after the first dose has been given and well before the effect of diuresis has taken pace. Studies of pulmonary mechanics have demonstrated improvement in both lung compliance and lung resistance. Most studies have used a dose of 1 mg/kg/day but some have suggested a dose of Img/kg every other day demonstrating a sustained improvement in pulmonary function with fewer side effects. Thiazides and spironolactone31 can be used in combination with furosemide to decrease the side effects of the later.

Bronchodilators (<xref ref-type="bibr" rid="bib032">32</xref>)

Inadequate data exist to recommend the use of beta agonists, ipratropium bromide or methylxanthines for BPD. Beta agonists and methylxanthines, however have been shown to produce short-term improvements in lung mechanics. Salbutamol has been the beta agonist of choice.

Respiratory syncytial virus (RSV) immune globulin

(33) Prophylaxis with RSV immune globulin significantly decreases the incidence of RSV infection and need for hospitalization, but don’t prevent ventilation. However, before advising this modality of treatment, locally prevalent viruses needs to be studied first.

Parental counseling

Counseling of parents of infants with BPD should focus on its natural history, medical implications and complications, early signs of respiratory decompensation so as to seek urgent medical attention, handling of respiratory emergencies, awareness of environmental irritants and minimization of infection risk, effect of chronic disease on family dynamics. It is imperative to reassure the parents that most infants with BPD do recover and that the frequently cited sequelae are potentially not life threatening or handicapping.

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