Pharmacological strategies in the prevention and management of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a disease of complex and multifactorial etiology and a major cause of morbidity in premature infants. Contributing factors include infection, exposure to toxic oxygen levels, and ventilator-induced lung injury, resulting in arrested lung development and impaired lung function. Several preventive and therapeutic strategies have been employed and include lung protective ventilator strategies, pharmacological and nutritional interventions. These strategies target different components and stages of the disease process, and their success has been variable. This review intends to bring together prior and current pharmacological interventions and future therapeutic modalities that appear promising in the prevention and management of BPD. Better understanding of the pathogenesis has given hope for newer treatment options. Newer studies need to be designed to assess the efficacy of combination therapies that target multiple steps of the disease process.

[1]  D. Stevenson.  Low-Dose Dexamethasone Facilitates Extubation Among Chronically Ventilator-Dependent Infants: A Multicenter, International, Randomized, Controlled Trial , 2007 .

[2]  H. Halliday,et al.  Inhaled versus systemic corticosteroids for the treatment of chronic lung disease in ventilated very low birth weight preterm infants. , 2007, The Cochrane database of systematic reviews.

[3]  J. Carlin,et al.  Low-Dose Dexamethasone Facilitates Extubation Among Chronically Ventilator-Dependent Infants: A Multicenter, International, Randomized, Controlled Trial , 2006, Pediatrics.

[4]  D. Dewitte.  Neurodevelopmental Outcomes of Premature Infants Treated With Inhaled Nitric Oxide , 2006 .

[5]  A. Zander,et al.  Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats. , 2005, Kidney international.

[6]  R. Mitchell,et al.  The role of stem cells in the response to myocardial and vascular wall injury. , 2005, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[7]  W. Poole,et al.  Inhaled nitric oxide for premature infants with severe respiratory failure. , 2005, The New England journal of medicine.

[8]  M. Rojas,et al.  Bone marrow-derived mesenchymal stem cells in repair of the injured lung. , 2005, American journal of respiratory cell and molecular biology.

[9]  C. Lachance,et al.  Fluticasone Inhalation in Moderate Cases of Bronchopulmonary Dysplasia , 2005, Pediatrics.

[10]  D. Phinney,et al.  Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. , 2005, Current pharmaceutical design.

[11]  C. Aebi,et al.  Respiratory response to salbutamol (albuterol) in ventilator-dependent infants with chronic lung disease: pressurized aerosol delivery versus intravenous injection , 1993, Intensive Care Medicine.

[12]  P. Taylor,et al.  J Soc Gynecol Investig , 2005 .

[13]  K. Stenmark,et al.  Lung vascular development: implications for the pathogenesis of bronchopulmonary dysplasia. , 2005, Annual review of physiology.

[14]  K. Watterberg,et al.  Prophylaxis of Early Adrenal Insufficiency to Prevent Bronchopulmonary Dysplasia: A Multicenter Trial , 2004, Pediatrics.

[15]  V. Fellman,et al.  N-Acetylcysteine Administration during the First Week of Life Does Not Improve Lung Function in Extremely Low Birth Weight Infants , 2004, Neonatology.

[16]  F. Walther,et al.  Pentoxifylline reduces fibrin deposition and prolongs survival in neonatal hyperoxic lung injury. , 2004, Journal of applied physiology.

[17]  V. Baum.  Oxygen-Saturation Targets and Outcomes in Extremely Preterm Infants , 2004 .

[18]  C. Piantadosi,et al.  Discordant extracellular superoxide dismutase expression and activity in neonatal hyperoxic lung. , 2004, American journal of respiratory and critical care medicine.

[19]  Jesse D. Roberts,et al.  Inhaled Nitric Oxide A Selective Pulmonary Vasodilator Current Uses and Therapeutic Potential , 2004 .

[20]  A. Jobe,et al.  Choice and dose of corticosteroid for antenatal treatments. , 2004, American journal of obstetrics and gynecology.

[21]  K. Stenmark,et al.  Predisposition of infants with chronic lung disease to respiratory syncytial virus-induced respiratory failure: a vascular hypothesis , 2004, The Pediatric infectious disease journal.

[22]  B. Lipworth,et al.  Acute systemic effects of inhaled salbutamol in asthmatic subjects expressing common homozygous beta2-adrenoceptor haplotypes at positions 16 and 27. , 2003, British journal of clinical pharmacology.

[23]  B. Silke.  Central hemodynamic effects of diuretic therapy in chronic heart failure , 2004, Cardiovascular Drugs and Therapy.

[24]  A. Ohlsson,et al.  Inositol for respiratory distress syndrome in preterm infants. , 2012, The Cochrane database of systematic reviews.

[25]  V. Fellman,et al.  N-acetylcysteine does not prevent bronchopulmonary dysplasia in immature infants: a randomized controlled trial. , 2003, The Journal of pediatrics.

[26]  N. Laird,et al.  Family-based association analysis of beta2-adrenergic receptor polymorphisms in the childhood asthma management program. , 2003, The Journal of allergy and clinical immunology.

[27]  D. Phelps,et al.  Erythromycin for the prevention of chronic lung disease in intubated preterm infants at risk for, or colonized or infected with Ureaplasma urealyticum. , 2003, The Cochrane database of systematic reviews.

[28]  D. D. Ourth,et al.  Ureaplasma in lung. 1. Localization by in situ hybridization in a mouse model. , 2003, Experimental and molecular pathology.

[29]  D. D. Ourth,et al.  Ureaplasma in lung. 2. Association with bronchopulmonary dysplasia in premature newborns. , 2003, Experimental and molecular pathology.

[30]  J. Loggins,et al.  Failure of erythromycin to eliminate airway colonization with ureaplasma urealyticum in very low birth weight infants , 2003, BMC pediatrics.

[31]  J. Davis,et al.  Pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human CuZn superoxide dismutase. , 2003, Pediatrics.

[32]  K. Stenmark,et al.  Lung vascular development: breathing new life into an old problem. , 2003, American journal of respiratory cell and molecular biology.

[33]  H. Halliday,et al.  Inhaled versus systemic corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates. , 2003, The Cochrane database of systematic reviews.

[34]  L. Doyle,et al.  Early postnatal (<96 hours) corticosteroids for preventing chronic lung disease in preterm infants. , 2003, The Cochrane database of systematic reviews.

[35]  L. Brion,et al.  Intravenous or enteral loop diuretics for preterm infants with (or developing) chronic lung disease. , 2011, The Cochrane database of systematic reviews.

[36]  J. Cummings,et al.  A Randomized Trial of Inhaled Versus Intravenous Steroids in Ventilator-Dependent Preterm Infants , 2002, Journal of Perinatology.

[37]  G. Cassell,et al.  Lung Pathology in Premature Infants with Ureaplasma urealyticum Infection , 2002, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[38]  M. Kennedy,et al.  Beta-adrenergic receptor polymorphisms and drug responses in asthma. , 2002, Pharmacogenomics.

[39]  L. Brion,et al.  Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease. , 2002, The Cochrane database of systematic reviews.

[40]  R. Ehrenkranz,et al.  Early postnatal (<96 hours) corticosteroids for preventing chronic lung disease in preterm infants. , 2003, The Cochrane database of systematic reviews.

[41]  P. Gressens,et al.  Neurotoxic Effects of Fluorinated Glucocorticoid Preparations on the Developing Mouse Brain: Role of Preservatives , 2001, Pediatric Research.

[42]  Neil D. Theise,et al.  Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem Cell , 2001, Cell.

[43]  V. Bhandari,et al.  A prospective controlled trial of albuterol aerosol delivered via metered dose inhaler-spacer device (MDI) versus jet nebulizer in ventilated preterm neonates. , 2001, American journal of perinatology.

[44]  C. Patterson,et al.  A multicenter, randomized open study of early corticosteroid treatment (OSECT) in preterm infants with respiratory illness: comparison of early and late treatment and of dexamethasone and inhaled budesonide. , 2001, Pediatrics.

[45]  L. Brion,et al.  Aerosolized diuretics for preterm infants with (or developing) chronic lung disease. , 2006, The Cochrane database of systematic reviews.

[46]  R. Ehrenkranz,et al.  Delayed (>3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants. , 2003, The Cochrane database of systematic reviews.

[47]  B. Darlow,et al.  Vitamin A supplementation for preventing morbidity and mortality in very low birthweight infants. , 2002, The Cochrane database of systematic reviews.

[48]  J. Fiascone,et al.  Strategies for prevention of neonatal chronic lung disease. , 2000, Seminars in perinatology.

[49]  N. Berman,et al.  Postnatal Thyroxine Supplementation in Infants Less Than 32 Weeks' Gestation: Effects on Pulmonary Morbidity , 2000, Journal of Perinatology.

[50]  J. Flynn,et al.  Supplemental Therapeutic Oxygen for Prethreshold Retinopathy Of Prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes. , 2000, Pediatrics.

[51]  F. Ducharme,et al.  Inhaled steroids for neonatal chronic lung disease. , 1999, The Cochrane database of systematic reviews.

[52]  S. Abbasi,et al.  Pulmonary Function and Electrolyte Balance Following Spironolactone Treatment in Preterm Infants With Chronic Lung Disease: A Double-Blind, Placebo-Controlled, Randomized Trial , 2000, Journal of Perinatology.

[53]  W. Hurford,et al.  Inhaled nitric oxide: basic biology and clinical applications. , 1999, Anesthesiology.

[54]  D. Cox,et al.  Functional and Antigenic Concentrations of Alpha-1-Proteinase Inhibitor after Administration for the Prevention of Chronic Lung Disease of Prematurity , 1999, Neonatology.

[55]  R. Lauterbach,et al.  Nebulized pentoxifylline in successful treatment of five premature neonates with bronchopulmonary dysplasia , 1999, European Journal of Pediatrics.

[56]  J. Rychik,et al.  Changes in oxygenation with inhaled nitric oxide in severe bronchopulmonary dysplasia. , 1999, Pediatrics.

[57]  A. Denjean,et al.  Inhaled salbutamol and beclomethasone for preventing broncho-pulmonary dysplasia: a randomised double-blind study , 1998, European Journal of Pediatrics.

[58]  G. Faxelius,et al.  Ureaplasma urealyticum, erythromycin and respiratory morbidity in high‐risk preterm neonates , 1998, Acta paediatrica.

[59]  A. Husain,et al.  Pathology of arrested acinar development in postsurfactant bronchopulmonary dysplasia. , 1998, Human pathology.

[60]  N. Rifai,et al.  Early High Dose Antioxidant Vitamins Do Not Prevent Bronchopulmonary Dysplasia in Premature Baboons Exposed to Prolonged Hyperosia: APilot Study , 1998, Pediatric Research.

[61]  T. Shaffer,et al.  Antenatal Triiodothyronine Improves Neonatal Pulmonary Function in Preterm Lambs , 1998, The Journal of the Society for Gynecologic Investigation: JSGI.

[62]  D. Cox,et al.  α1-Proteinase Inhibitor Therapy for the Prevention of Chronic Lung Disease of Prematurity: A Randomized, Controlled Trial , 1998, Pediatrics.

[63]  N. McIntosh,et al.  Randomised trial of erythromycin on the development of chronic lung disease in preterm infants , 1998, Archives of disease in childhood. Fetal and neonatal edition.

[64]  M. Keszler,et al.  Pulmonary function changes after nebulised and intravenous frusemide in ventilated premature infants , 1997, Archives of disease in childhood. Fetal and neonatal edition.

[65]  C. Poets,et al.  Effects of salbutamol delivery from a metered dose inhaler versus jet nebulizer on dynamic lung mechanics in very preterm infants with chronic lung disease , 1997, Pediatric pulmonology.

[66]  Richard J Martin,et al.  Effect of Exogenous and Endogenous Nitric Oxide on the Airway and Tissue Components of Lung Resistance in the Newborn Piglet , 1997, Pediatric Research.

[67]  E. Bell,et al.  Changes in body water compartments with diuretic therapy in infants with chronic lung disease. , 1997, Early human development.

[68]  M. O'Doherty,et al.  Comparison of jet and ultrasonic nebulizer pulmonary aerosol deposition during mechanical ventilation. , 1997, The European respiratory journal.

[69]  V. Bhutani,et al.  Pulmonary Function and Electrolyte Balance Following Spironolactone Treatment in Preterm Infants with Chronic Lung Disease. • 321 , 1997, Pediatric Research.

[70]  G. Coates,et al.  Pulmonary Deposition of Salbutamol Aerosol Delivered by Metered Dose Inhaler, Jet Nebulizer, and Ultrasonic Nebulizer in Mechanically Ventilated Rabbits , 1994, Pediatric Research.

[71]  J. Hasday,et al.  Cromolyn sodium prophylaxis inhibits pulmonary proinflammatory cytokines in infants at high risk for bronchopulmonary dysplasia. , 1997, American journal of respiratory and critical care medicine.

[72]  G. Coates,et al.  Efficiency of aerosol medication delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia , 1996, Pediatric pulmonology.

[73]  N. McIntosh,et al.  Infection with Ureaplasma urealyticum and Mycoplasma hominis and the development of chronic lung disease in preterm infants , 1996, Acta paediatrica.

[74]  P. Diot,et al.  Albuterol delivery in a model of mechanical ventilation. Comparison of metered-dose inhaler and nebulizer efficiency. , 1995, American journal of respiratory and critical care medicine.

[75]  J. Kellner,et al.  Association of Ureaplasma urealyticum colonization with chronic lung disease of prematurity: results of a metaanalysis. , 1995, The Journal of pediatrics.

[76]  R. Cooke,et al.  Randomised controlled trial of allopurinol prophylaxis in very preterm infants. , 1995, Archives of disease in childhood. Fetal and neonatal edition.

[77]  J. Zimmerman.  Bronchoalveolar inflammatory pathophysiology of bronchopulmonary dysplasia. , 1995, Clinics in perinatology.

[78]  A. Meister,et al.  L-2-oxothiazolidine-4-carboxylate, a cysteine precursor, stimulates growth and normalizes tissue glutathione concentrations in rats fed a sulfur amino acid-deficient diet. , 1995, The Journal of nutrition.

[79]  M. O'Doherty,et al.  Effect of a spacer on pulmonary aerosol deposition from a jet nebuliser during mechanical ventilation. , 1995, Thorax.

[80]  R. Pildes,et al.  Nebulized furosemide in infants with bronchopulmonary dysplasia. , 1994, The Journal of pediatrics.

[81]  D. Durand,et al.  Randomized trial of long-term diuretic therapy for infants with oxygen-dependent bronchopulmonary dysplasia. , 1994, The Journal of pediatrics.

[82]  J. Davis,et al.  Prophylactic effects of recombinant human superoxide dismutase in neonatal lung injury. , 1993, Journal of applied physiology.

[83]  K. Watterberg,et al.  Failure of cromolyn sodium to reduce the incidence of bronchopulmonary dysplasia: a pilot study. The Neonatal Cromolyn Study Group. , 1993, Pediatrics.

[84]  E. Bell,et al.  Addition of metolazone to overcome tolerance to furosemide in infants with bronchopulmonary dysplasia. , 1992, The Journal of pediatrics.

[85]  K. Hoppu,et al.  Inositol supplementation in premature infants with respiratory distress syndrome. , 1992, The New England journal of medicine.

[86]  A. Zipursky,et al.  Failure of supplementation with vitamin E to prevent bronchopulmonary dysplasia in infants less than 1,500 g birth weight. , 1991, The European respiratory journal.

[87]  M. Xanthou,et al.  A trial of vitamin A supplementation for the prevention of intraventricular hemorrhage in very low birth weight neonates. , 1991, Journal of perinatal medicine.

[88]  B. Schmidt,et al.  Respiratory response and pharmacokinetics of intravenous salbutamol in infants with bronchopulmonary dysplasia , 1990, Critical care medicine.

[89]  R. Parker,et al.  Double-blind, placebo-controlled trial of alternate-day furosemide therapy in infants with chronic bronchopulmonary dysplasia. , 1990, The Journal of pediatrics.

[90]  A. Leviton,et al.  Hydration during the first days of life and the risk of bronchopulmonary dysplasia in low birth weight infants. , 1990, The Journal of pediatrics.

[91]  J. Davis,et al.  Drug therapy for bronchopulmonary dysplasia , 1990, Pediatric pulmonology.

[92]  A. Rotschild,et al.  Randomized, double-blind, controlled trial of long-term diuretic therapy for bronchopulmonary dysplasia. , 1989, The Journal of pediatrics.

[93]  C. Lundergan,et al.  Effect of cyclooxygenase inhibition on the pulmonary vasodilator response to furosemide. , 1988, The Journal of pharmacology and experimental therapeutics.

[94]  J. Ali,et al.  Colloid osmotic pressure in pulmonary edema clearance with furosemide. , 1987, Chest.

[95]  K. Kennedy,et al.  Clinical trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia. , 1987, The Journal of pediatrics.

[96]  S. Devaskar,et al.  Transplacental stimulation of fetal lung maturation: effect of triiodothyronine in the female and male rabbit fetus. , 1987, Biology of the neonate.

[97]  I. Zabaleta,et al.  Serial trypsin inhibitory capacity and ceruloplasmin levels in prematures at risk for bronchopulmonary dysplasia. , 1986, The American review of respiratory disease.

[98]  S. Cassin,et al.  The Effects of Bumetanide and Furosemide on Lung Liquid Secretion in Fetal Sheep 1 , 1986, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[99]  I. Liener,et al.  Protection against pulmonary oxygen toxicity in rats by the intratracheal administration of liposome-encapsulated superoxide dismutase or catalase. , 2015, The American review of respiratory disease.

[100]  J. Brady,et al.  Controlled trial of furosemide therapy in infants with chronic lung disease. , 1985, The Journal of pediatrics.

[101]  P. Barnes,et al.  Fetal pulmonary beta-adrenergic receptors: characterization in the human and in vitro modulation by glucocorticoids in the rabbit. , 1985, Pediatric pulmonology.

[102]  R. Wolfe,et al.  Pulmonary vascular response to oxygen in infants with severe bronchopulmonary dysplasia. , 1985, Pediatrics.

[103]  John D. Johnson,et al.  Neonatal lung neutrophils and elastase/proteinase inhibitor imbalance. , 2015, The American review of respiratory disease.

[104]  T. Keens,et al.  Effect of oral diuretics on pulmonary mechanics in infants with chronic bronchopulmonary dysplasia: results of a double-blind crossover sequential trial. , 1984, Pediatrics.

[105]  J. Crapo,et al.  Protection against oxygen toxicity by intravenous injection of liposome-entrapped catalase and superoxide dismutase. , 1984, The Journal of clinical investigation.

[106]  D. Strayer,et al.  Elastase and alpha 1-proteinase inhibitor activity in tracheal aspirates during respiratory distress syndrome. Role of inflammation in the pathogenesis of bronchopulmonary dysplasia. , 1983, The Journal of clinical investigation.

[107]  A. Lazzara,et al.  Pulmonary effects of furosemide in preterm infants with lung disease. , 1983, The Journal of pediatrics.

[108]  Gerber Jg.  Role of prostaglandins in the hemodynamic and tubular effects of furosemide. , 1983 .

[109]  J. Gerber.  Role of prostaglandins in the hemodynamic and tubular effects of furosemide. , 1983, Federation proceedings.

[110]  D. Strandness,et al.  Pentoxifylline efficacy in the treatment of intermittent claudication: multicenter controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients. , 1982, American heart journal.

[111]  G. Gregory,et al.  Colloid osmotic pressure of normal newborns and premature infants , 1981, Critical care medicine.

[112]  N. Reichek,et al.  Effect of diuresis on the performance of the failing left ventricle in man. , 1981, The American journal of medicine.

[113]  R. Demling,et al.  The effect of furosemide on the pulmonary transvascular fluid filtration rate , 1978, Critical care medicine.

[114]  A. Stark,et al.  Bronchopulmonary dysplasia: possible relationship to pulmonary edema. , 1978, The Journal of pediatrics.

[115]  J. Forrester,et al.  Renal and extrarenal hemodynamic effects of furosemide in congestive heart failure after acute myocardial infarction. , 1973, The New England journal of medicine.