BRONCHOPULMONARY DYSPLASIA a neonatal problem.pptx

UG medical teaching

1. BRONCHOPULMONARY DYSPLASIA

2. PMA Post-menstrual age: A measure of the age of an infant that combines gestational and postnatal age, both in weeks. For example, a 23-week gestational age infant at 9 weeks after birth has a postmenstrual age of 32 weeks.

3. Historical perspectives The term BPD was first coined in 1967 when Northway  et al . outlined the previously undescribed sequelae of RDS ( prolongrd oxygen dependency) based upon a large group of preterm infants. Based on this paper, over the next two decades, the definition of BPD was “an oxygen requirement at 28 days of life”. When bronchopulmonary dysplasia (BPD) was first described Northway, the use of assisted ventilation in neonates was in its infancy. High concentrations of oxygen were implicated, and BPD was equated with ‘pulmonary oxygen toxicity’. Later, the potential role of antenatal steroids for lung maturation, the development of surfactant therapy, continuous positive airway pressure, have dramatically improved the survival of extremely preterm infants . The concept of BPD shifted from postnatal lung injury ( classic BPD) to antenatal lung maturation (New BPD).

4. Historical perspectives The need for new look into pathogenesis and definition of BPD lead to several studies. The disease pattern that existed before the introduction of AN steroid and surfactant therapy and reported by Northway  et al became known as “classic BPD”. The disease pattern that emerged after the advent of surfactant therapy, AN steroid, CPAP and gentler ventilation was described as “new BPD” and was the result of improved antenatal lung maturation due to interventions in preterm delivaries .

5. Classic Versus New BPD The old or “classic” form of BPD was described by Northway in 1967 during the presurfactant era and prior to the use of safe mechanical ventilation strategies . Classic bronchopulmonary dysplasia (BPD) was defined as persistent oxygen dependency up to 28 days of life. It consisted of tissue damage in both airways and alveoli. Extremely preterm infants born at less than 28 weeks’ gestation are at risk to develop “new” BPD and arrest of lung development, which is characterized by alveolar simplification and vascular hypoplasia that can lead to impaired gas exchange.

6. Classic bronchopulmonary dysplasia (Classic BPD ) The classic BPD was defined as a chronic lung disease that occurs in premature infants who had respiratory distress after birth, require oxygen supplementation or mechanical ventilator support at 28 postnatal days or 36 weeks postmenstrual age (PMA). Stage I: (2-3 days) is a period of acute RDS. The radiologic picture is similar to RDS. Stage II: (4-10 days) is a period of regeneration. The chest radiograph shows complete opacity of the lung obscuring the heart and lung borders. Stage III: (10-20 days) is a period of transition to chronic disease. The early radiographic changes are replaced by areas of coarse, irregular shaped densities and areas of cyst lesions. Areas of density are caused by interstitial edema or atelectasis due to obstruction of small bronchioles with luminal debris. The cysts represent foci of emphysema. Stage IV: (beyond 1 month) is a period of chronic disease. Chest radiograph shows large cysts and marked fibrosis and edema with areas of consolidation and areas of over inflation .

7. New bronchopulmonary dysplasia (New BPD) BPD is now defined clinically as a chronic lung disease occurring in premature infants who need for supplemental O2 for at least 28 days after birth, and its severity is graded according to the oxygen concentration and positive pressure of respiratory support at near term. For gestation age 32 weeks or more, this time determination varies between 28 days to 56 days before discharge. For gestation age less than 32 week, the time of determination is 36 weeks postmenstrual age. A physiologic test such as pulse oximetry saturation is recommended to confirm the requirement of oxygen supplementation at the time of assessment.

8. New BPD Gestation age < 32 weeks > 32 weeks Time of assessment 36 wk PMA or discharge to home, whichever comes first 28 d to 56 d postnatal age or discharge to home, whichever comes first Treatment with oxygen > 21% for at least 28 d plus Mild BPD Breathing room air at 36 wk PMA or discharge, whichever comes first Breathing room air by 56 d postnatal age or discharge, whichever comes first Moderate BPD Need for <30% oxygen at 36 PMA or discharge, whichever comes first Need for > 30% oxygen and/or positive pressure (PPV or NCPAP) at 56 d postnatal age or discharge, whichever comes first Severe BPD   Need† for ≥30% oxygen and/or positive pressure (PPV or NCPAP) at 36 wk postmenstrual age or discharge home, whichever comes first   Need† for ≥30% oxygen and/or positive pressure (PPV or NCPAP) at 56 days postnatal age or discharge home, whichever comes first

9. Pathology of bronchopumonary dysplasia The characteristic changes of classic BPD are airway injury and inflammation, airway epithelial cell metaplasia, and parenchymal fibrosis. In contrast, the characteristic morphology of “new” BPD is disruption of lung development

10. Pathogenesis The pathogenesis of BPD is multifactorial. The original concepts of risk factors include: prematurity ; respiratory distress; mechanical ventilation; oxygen supplementation . These factors still play an important role in the development of new BPD. However, infection and inflammation, pulmonary edema as result of and patent ductus arteriosus (PDA) or fluid overloading, nutritional deficiencies and genetic factors may also contribute to lung injury. Classic BPD is heavily influenced by injury inflammation and fibrosis; while new primarily is an arrest of development, disorder or delayed modeling and remodeling.

11. Prematurity Most of these infants need supplemental oxygen and assisted ventilation after birth to achieve adequate gas exchange. Infants born at 23-28 weeks gestation are just beginning to alveolarize the distal saccule of the lung in parallel with the development of the alveolar capillary bed. Alveolar development can be delayed with hypoxia, hyperoxia , inflammations, glucocorticoids, and poor nutrition. Patent ductus arteriosus (PDA) is present in most ELBW infants. PDA shunt increases pulmonary blood flow, and may result in pulmonary edema. Oxygen toxicity Any concentration in excess of room air might increase the risk of lung damage when administered over a period of time. Early pulmonary change caused by oxygen toxicity consists of atelectasis, edema, alveolar hemorrhage, inflammation .

12. Mechanical ventilation-barotrauma and volutrauma Barotrauma is the lung injury caused by the pressure used to inflate the lung Barotrauma produces alveolar shear stress, disruption of alveolarization , pulmonary air leak, and release of damaging cytokine and other biologically substances. High ventilator pressure has long been considered as a major cause of BPD, but tissue damage is now more attributed to over-distension of the lung from high tidal volume ventilation ( volutrauma ). Inflammation Inflammation plays the central role in the development of BPD. Inflammatory reaction may be triggered by factors including infection before or after birth, oxygen free radicals, barotraumas or volutrauma from mechanical ventilation, and pulmonary edema . Pulmonary inflammation affects normal alveolization and angiogenesis, these may further lead to remodeling of developing lung resulting in BPD.

13. Chorioamnionitis : Premature infants who were exposed to maternal chorioamnionitis and required mechanical ventilation after birth have higher incidence of BPD. Several studies have suggested an association between Ureaplasma urealyticum tracheal colonization and the development of severe respiratory failure and BPD in very low birth weight infants Postnatal infection Intubated infants are prone to develop nosocomial infection with deteriorating gas exchange, and are at great risk for development of BPD. Pulmonary edema, patent ductus arteriosus and fluid overloading Increases pulmonary blood flow from left-to-right shunt blood flow crossing patent ductus arteriosus may result increasing interstitial fluid and pulmonary edema. Pulmonary compliance is reduced and resistance is increased, creating a need for prolonged ventilator support with higher oxygen concentration and ventilation pressure

14. Nutrition , Vitamin A Inadequate nutrition may amplify the lung injury of mechanical ventilation, oxygen toxicity and hinder the repair and recovery course. Vitamin A deficiency may promote chronic lung disease by impairing lung healing, increasing the loss of cilia and squamous-cell metaplasia, increasing susceptibility to infection, and decreasing the number of alveoli. Genetics Lung development is regulated by a variety of genes that balance between pro- and anti inflammation , oxygen toxicity, cell injury and death, tissue repair, and infection . Specific genes that are known to be involved in these biologic pathways have been evaluated for their potential contribution to BPD.

15. CLINICAL MANIFESTATIONS The infants present with intermittent cyanotic or life-threatening episodes—“BPD spells”, tachypnea, retractions, and rales on auscultation. Arterial blood gas (ABG) analysis shows hypoxemia and hypercarbia The chest radiograph: With “new” BPD, the initial appearance is often diffuse haziness, increased density, and normal- to-low lung volumes. In more severe disease, chronic changes may include inhomogeneous regions of opacification and hyperlucency with superimposed hyperinflation. Cardiac evaluation: Electrocardiogram (ECG) can show persistent or progressive right ventricular hypertrophy if cor pulmonale develops. Left ventricular hypertrophy may develop with systemic hypertension

16. Infant pulmonary function testing ( iPFT ). Increased respiratory system resistance ( Rrs ) and decreased dynamic compliance ( Crs ) are hallmarks of BPD. In the first year after birth, iPFTs reveal decreased forced expiratory flow rate, increased functional residual capacity (FRC), increased residual volume (RV), and increased RV/total lung capacity ratio and bronchodilator responsiveness, with an overall pattern of mild-to-moderate airflow obstruction, air trapping, and increased airway reactivity.

17. BPD SCREENING Infants with a persistent need of respiratory support at 10 to 14 days of age are at the highest risk of BPD at 36 weeks. Postnatal nutritional deficit is an independent predictor of BPD. NTproBNP at 14 days of life could be used as an early marker of later BPD. Ongoing research has identified several biomarkers in the blood, tracheal aspirates, and even urine which could predict BPD and thereby identify infants who would benefit from preventive therapy. However, most have a low predictive accuracy. In recent years, newer systems-biology-based “ omic ” approaches, including but not limited to genomics, microbiomics , proteomics, and metabolomics, have helped several novel biomarkers in BPD that may improve the prediction of BPD.

18. Treatment Vitamin A (5,000 IU intramuscular [IM], three times weekly for the first 28 days of age) reduced the incidence of CLD in extremely low-birth-weight (ELBW) infants by 10%. One trial has found benefit with oral vitamin A given as a syrup 10,000 units/dose on alternate days for 28 days. Caffeine citrate (20 mg/kg loading dose and 5 mg/kg daily maintenance) started during the first 10 days after birth in infants 500 to 1,250 g birth weight reduced the rate of BPD from 47% to 36% and improved the rate of survival without neurodevelopmental disability at 18 to 21 months corrected age . Recent evidence suggests that beginning caffeine therapy within the first 72 hours of age and a higher loading and maintenance dose results in the greatest reduction in the BPD risk.

19. Postnatal steroids Although the most recent meta-analysis on early dexamethasone (<8 days) found reduced BPD risk, it is not recommended due to unacceptable side effects such as GI perforation, hypertrophic cardiomyopathy, cerebral palsy, and major neurosensory disability. Randomized trials of systemic hydrocortisone started in the first week have found a reduced risk of BPD. However, a subgroup analysis found higher sepsis rates among the most preterm infants (24 to 25 weeks) treated with hydrocortisone. The meta-analysis of inhaled steroids demonstrates improved BPD-free survival. However, in the largest trial in the meta-analysis— the NEuroSIS trial—the decreased BPD rates among survivors were at the expense of greater mortality. However, intratracheal budesonide combined with surfactant holds promise in preventing BPD.

20. Investigational therapies without proven efficacy Inhaled nitric oxide ( iNO ). Considering lack of robust evidence and also logistics of continuous treatment with an inhalational medication, iNO is not recommended as a preventive strategy for BPD. In a small phase II trial, treatment with recombinant human IGF in combination with its binding protein reduced the risk of severe BPD . Mesenchymal stem cells (MSCs) protect and repair lung injury by preventing lung inflammation. Bone marrow– and cord blood–derived MSCs are being evaluated in human trials for the prevention of BPD. Whether azithromycin may decrease the risk of developing BPD in infants with documented Ureaplasma colonization or infection is under investigation.

21. Mechanical ventilation One important strategy to reduce BPD is to minimize invasive ventilation . The American Academy of Pediatrics Committee on Fetus and Newborn recommends early use of CPAP with subsequent selective surfactant administration in extremely preterm infants as an evidence-based strategy to reduce the risk for death or BPD. Nasal intermittent positive pressure ventilation (NIPPV) after extubation may further improve this benefit. HHHFNC therapy may decrease the risk of extubation failure with the additional benefit of inducing less nasal trauma as compared to CPAP.

22. Supplemental oxygen One approach for infants who receive supplemental oxygen is to target SpO2 at 92% to 95% with alarm limits at 84% to 96%. Another is to adjust the target saturations according to gestational age or PMA. In general, SpO2 should remain >90% during sleep , feedings, and active periods before supplemental O2 is discontinued. An “oxygen challenge test” can be performed at 36 weeks’ PMA to confirm whether an infant requires supplemental oxygen to maintain SpO2 >90% and thus meets the physiologic definition of BPD.

23. Surfactant replacement therapy decreases the combined outcome of O2 requirement or death at 28 days of age, although it has made little or no impact on the overall incidence of BPD. Breast milk is the preferred nutrition for all preterm infants. In addition to the known reduction in necrotizing enterocolitis (NEC) and late-onset sepsis, recent observational studies have shown that it reduces the risk of BPD. T reatment of a hemodynamically significant PDA in infants who have respiratory decompensation or cannot be weaned from mechanical ventilation . Initial fluid intake is limited to the minimum required. Initially, we provide intake adequate to maintain urine output of at least 1 mL/ kg/hour and serum sodium concentration of 140 to 145 mEq /L.

24. Medications Diuretics are used to treat pulmonary fluid retention. Furosemide is used initially at a dose of 1.0 mg/kg intravenously (or 2 mg/kg PO/ pg ) daily. Chlorothiazide (20 to 40 mg/kg/day orally, divided BID) or hydrochlorothiazide (2 to 4 mg/kg/ day orally, divided BID) to avoid furosemide toxicities. Bronchodilators . Administration of nebulized β-adrenergic agonists (BAAs) such as albuterol Nebulized (25 mg/kg/dose) ipratropium bromide, a muscarinic agent, increases Crs and decreases Rrs . Caffeine citrate. The methylxanthine caffeine has airway dilation effects in asthmatics similar to aminophylline. This response has not been studied in the setting of BPD. Steroids . A short course of oral steroids is often used during BPD “exacerbation” or intercurrent viral illness to reduce work of breathing or to wean off supplemental oxygen.

25. Monitoring continuous pulse oximetry for long-term monitoring of infants with BPD. The long-term goal is to keep the saturation >90 (PaO2 ≥55 mm Hg) and avoid hyperoxemia (saturation 95 ). Capillary blood gas (CBG) values are useful to monitor pH and PCO2. Transcutaneous PCO2 monitors may be useful to monitor PCO2 trends, which allow more real-time ventilator adjustment to both minimize barotrauma and respond earlier to decompensations. Pulmonary function testing is used in some centers to document functional responses to trials of bronchodilators and diuretics.

26. Nutrition Early administration of fish oil–containing lipid emulsions reduces inflammatory mediators IL-1β and IL-6 and is associated with a shorter duration of ventilatory support and less BPD. As enteral feeding is started, we feed by orogastric or nasogastric tube and advance oral feeding gradually to avoid tiring the infant. Increase the caloric density from 24 to 30 cal / oz human milk or formula, as required, to maintain daily growth of at least 10 to 15 mg/kg.

27. COMPLICATIONS Trauma to the nasal septum, larynx, trachea, or bronchi is common after prolonged or repeated intubation and suctioning. Abnormalities include laryngotracheobronchomalacia , granulomas, vocal cord paresis, edema, ulceration with pseudomembranes , subglottic stenosis, and congenital structural anomalies. Pulmonary hypertension (PH) is a major complication of BPD that is associated with a 2-year mortality rate of 38% to 43% after diagnosis. Systemic hypertension , sometimes with left ventricular hypertrophy, may develop in infants with BPD receiving prolonged O2 therapy and should be treated. Left-to-right shunt through collateral vessels (e.g., bronchial arteries) can occur in BPD. Ureaplasma sp., Mycoplasma hominis and cytomegalovirus (CMV) infection has been associated with an increased risk of BPD. ROP . ELBW infants with BPD are at a high risk for developing ROP. Gastroesophageal reflux (GER).

28. OUTCOME Mortality in severe BPD is estimated at 10% to 20% during the first year of life. Tachypnea, retractions, dyspnea, cough, and wheezing can be seen for months to years in seriously affected children. Children with BPD have higher rates of motor, cognitive, educational, and behavioral impairments . Growth failure