e2 45 Gerhardt T, Bancalari E Apnea of prematurity I Lung function and regulation of breathing Pediatrics 1984;74 58 62 46 Martin RJ Pathophysiology of apnea of prematurity In Polin RA, Abman SH, Rowi[.]
e2 45 Gerhardt T, Bancalari E Apnea of prematurity I Lung function and regulation of breathing Pediatrics 1984;74:58-62 46 Martin RJ Pathophysiology of apnea of prematurity In: Polin RA, Abman SH, Rowitch DH, Benitz WE & Fox WW, eds Fetal & Neonatal Physiology 5th ed Philadelphia: Elsevier; 2016:1595-1604 47 Di Fiore JM, Arko MK, Miller MJ, et al Cardiorespiratory events in preterm infants referred for apnea monitoring studies Pediatrics 2001;108:1304-1308 48 Finer NN, Higgins R, Kattwinkel J, et al Summary proceedings from the apnea-of-prematurity group Pediatrics 2006;117: S47-S51 49 Di Fiore JM, Walsh M, Wrage L, et al Low oxygen saturation target range is associated with increased incidence of intermittent hypoxemia J Pediatr 2012;161:1047-1052 50 Sands SA, Edwards BA, Kelly VJ, et al Mechanism underlying accelerated arterial oxygen desaturation during recurrent apnea Am J Respir Crit Care Med 2010;182:961-969 51 Di Fiore JM, Bloom JN, Orge F, et al A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity J Pediatr 2010;157:69-73 52 Schmidt B, Whyte RK, Asztalos EV, et al Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial JAMA 2013;309:2111-2120 53 Poets CF, Roberts RS, Schmidt B, et al Association between intermittent hypoxemia or bradycardia and late death or disability in extremely preterm infants JAMA 2015;314:595-603 54 Kuzemko JA, Paala J Apnoeic attacks in the newborn treated with aminophylline Arch Dis Child 1973;48:404-406 55 Aranda JV, Gorman W, Bergsteinsson H, et al Efficacy of caffeine in treatment of apnea in the low-birth-weight infant J Pediatr 1977;90:467-472 56 Henderson-Smart DJ, Steer P Methylxanthine treatment for apnea in preterm infants Cochrane Database Syst Rev 2000;(2):CD000140 57 Schmidt B, Roberts RS, Davis P, et al Caffeine therapy for apnea of prematurity N Engl J Med 2006;354(20):2112-2121 58 Schmidt B, Roberts RS, Anderson PJ, et al Academic performance, motor function, and behavior 11 years after neonatal caffeine citrate therapy for apnea of prematurity: An 11-year follow-up of the CAP Randomized Clinical Trial JAMA Pediatr 2017;171(6):564-572 59 Abdel-Hady H, Nasef N, Shabaan AE, et al Caffeine therapy in preterm infants World J Clin Pediatr 2015;4:81-93 60 Eichenwald EC Apnea of prematurity Pediatrics 2016;137: e20153757-e20153757 61 Wilson CG, Martin RJ, Jaber M, et al Adenosine A2A receptors interact with GABAergic pathways to modulate respiration in neonatal piglets Respir Physiol Neurobiol 2004;141:201-211 62 Chardon K, Bach V, Telliez F, et al Effect of caffeine on peripheral chemoreceptor activity in premature neonates: interaction with sleep stages J Appl Physiol 2004;96:2161-2166 63 Kraaijenga JV, Hutten GJ, De Jongh FH, et al The effect of caffeine on diaphragmatic activity and tidal volume in preterm infants J Pediatr 2015;167:70-75 64 Köroğlu OA, MacFarlane PM, Balan KV, et al Anti-inflammatory effect of caffeine is associated with improved lung function after lipopolysaccharide-induced amnionitis Neonatology 2014;106: 235-240 65 Schmidt B, Roberts RS, Davis P, et al Long-term effects of caffeine therapy for apnea of prematurity N Engl J Med 2007;357:18931902 66 Schmidt B, Anderson PJ, Doyle LW, et al Survival without disability to age years after neonatal caffeine therapy for apnea of prematurity JAMA 2012;307:275-282 67 Diblasi RM Nasal continuous positive airway pressure (CPAP) for the respiratory care of the newborn infant Respir Care 2009;54:12091235 68 Pantalitschka T, Sievers J, Urschitz MS, et al Randomised crossover trial of four nasal respiratory support systems for apnoea of prematurity in very low birthweight infants Arch Dis Child Fetal Neonatal Ed 2009;94:F245-F248 69 Millar D, Kirpalani H Benefits of noninvasive ventilation Indian Pediatrics 2004;41:1008-1017 70 Zhao J, Gonzalez F, Mu D Apnea of prematurity: From cause to treatment Euro J Pediatr 2011;170:1097-1105 71 Deprest J, Brady P, Nicolaides K, et al Prenatal management of the fetus with isolated congenital diaphragmatic hernia in the era of the TOTAL trial Semin Fetal Neonatal Med 2014;19:338-348 72 McGivern MR, Best KE, Rankin J, et al Epidemiology of congenital diaphragmatic hernia in Europe: a register-based study Arch Dis Child Fetal Neonatal Ed 2015;100:F137-F144 73 Conrad SA, Rycus PT, Dalton H Extracorporeal Life Support Registry Report 2004 ASAIO J 2005;51:4-10 74 Schumacher RE, Baumgart S Extracorporeal membrane oxygenation 2001 The odyssey continues Clin Perinatol 2001;28: 629-653 75 Van Meurs K Is surfactant therapy beneficial in the treatment of the term newborn infant with congenital diaphragmatic hernia? J Pediatr 2004;145:312-316 76 Logan JW, Rice HE, Goldberg RN, et al Congenital diaphragmatic hernia: a systematic review and summary of best-evidence practice strategies J Perinatol 2007;27:535-549 77 Glick PL, Leach CL, Besner GE, et al Pathophysiology of congenital diaphragmatic hernia III: exogenous surfactant therapy for the high-risk neonate with CDH J Pediatr Surg 1992;27:866-869 78 Wilson JM, Di Fiore JM, Peters CA Experimental fetal tracheal ligation prevents the pulmonary hypoplasia associated with fetal nephrectomy: possible application for congenital diaphragmatic hernia J Pediatr Surg 1993;28:1433-1439, discussion 1439-1440 79 Di Fiore JM, Fauza DO, Slavin R, et al Experimental fetal tracheal ligation reverses the structural and physiological effects of pulmonary hypoplasia in congenital diaphragmatic hernia J Pediatr Surg 1994;29:248-256, discussion 56-257 80 Deprest J, Jani J, Van Schoubroeck D, et al Current consequences of prenatal diagnosis of congenital diaphragmatic hernia J Pediatr Surg 2006;41:423-430 81 Jelin E, Lee H Tracheal occlusion for fetal congenital diaphragmatic hernia: the US experience Clin Perinatol 2009;36:349-361 82 Ahmad A, Gangitano E, Odell RM, et al Survival, intracranial lesions, and neurodevelopmental outcome in infants with congenital diaphragmatic hernia treated with extracorporeal membrane oxygenation J Perinatol 1999;19(6 Pt 1):436-440 83 Cortes RA, Keller RL, Townsend T, et al Survival of severe congenital diaphragmatic hernia has morbid consequences J Pediatr Surg 2005;40:36-45, discussion 46 84 Rasheed A, Tindall S, Cueny DL, et al Neurodevelopmental outcome after congenital diaphragmatic hernia: extracorporeal membrane oxygenation before and after surgery J Pediatr Surg 2001;36:539-544 85 Robertson CM, Cheung PY, Haluschak MM, et al High prevalence of sensorineural hearing loss among survivors of neonatal congenital diaphragmatic hernia Western Canadian ECMO Follow-up Group Am J Otol 1998;19:730-736 86 Priest JR, Williams GM, Hill DA, et al Pulmonary cysts in early childhood and the risk of malignancy Pediatr Pulmonol 2009;44: 14-30 87 Gornall AS, Budd JL, Draper ES, et al Congenital cystic adenomatoid malformation: accuracy of prenatal diagnosis, prevalence and outcome in a general population Prenat Diagn 2003;23:997-1002 88 Wilson RD, Hedrick HL, Liechty KW, et al Cystic adenomatoid malformation of the lung: review of genetics, prenatal diagnosis, and in utero treatment Am J Med Genet A 2006;140:151-155 89 Stocker JT, Drake RM, Madewell JE Cystic and congenital lung disease in the newborn Perspect Pediatr Pathol 1978;4:93-154 90 van Koningsbruggen S, Ahrens F, Brockmann M, et al Congenital cystic adenomatoid malformation type Pediatr Pulmonol 2001; 32:471-475 e3 91 Stocker JT Congenital pulmonary airway malformation: a new name for and an expanded classification of congenital cystic adenomatoid malformation of the lung Histopathology 2002;41: 424-430 92 Usui N, Kamata S, Sawai T, et al Outcome predictors for infants with cystic lung disease J Pediatr Surg 2004;39:603-606 93 Crombleholme TM, Coleman B, Hedrick H, et al Cystic adenomatoid malformation volume ratio predicts outcome in prenatally diagnosed cystic adenomatoid malformation of the lung J Pediatr Surg 2002;37:331-338 94 Murphy JJ, Blair GK, Fraser GC, et al Rhabdomyosarcoma arising within congenital pulmonary cysts: report of three cases J Pediatr Surg 1992;27:1364-1367 95 Granata C, Gambini C, Balducci T, et al Bronchioloalveolar carcinoma arising in congenital cystic adenomatoid malformation in a child: a case report and review on malignancies originating in congenital cystic adenomatoid malformation Pediatr Pulmonol 1998;25:62-66 96 Limaiem F, Ayadi-Kaddour A, Djilani H, et al Pulmonary and mediastinal bronchogenic cysts: a clinicopathologic study of 33 cases Lung 2008;186:55-61 97 Correia-Pinto J, Gonzaga S, Huang Y, et al Congenital lung lesions-underlying molecular mechanisms Semin Pediatr Surg 2010;19:171-179 98 Stefanova P, Ivanov B Treatment of congenital lung cysts in childhood Khirurgiia 2014;75-79 99 Ribet ME, Copin MC, Gosselin B Bronchogenic cysts of the mediastinum J Thorac Cardiovasc Surg 1995;109:1003-1010 100 Corbett HJ, Humphrey GM Pulmonary sequestration Paediatr Respir Rev 2004;5:59-68 101 Hernanz-Schulman M Cysts and cystlike lesions of the lung Radiol Clin North Am 1993;31:631-649 102 Kravitz RM Congenital malformations of the lung Pediatr Clin North Am 1994;41:453-472 103 Duan M, Wang L, Cao Y, et al Results of surgical treatment of congenital cystic lung disease Thorac Cardiovasc Surg 2005;53:61-64 104 Bloom DC, Perkins JA, Manning SC Management of lymphatic malformations Curr Opin Otolaryngol Head Neck Surg 2004;12: 500-504 105 Northway WH Jr, Rosan RC, Porter DY Pulmonary disease following respirator therapy of hyaline-membrane disease Bronchopulmonary dysplasia N Engl J Med 1967;276(7):357-368 106 Stoll BJ, Hansen NI, Bell EF, et al Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012 JAMA 2015;314(10):1039-1051 107 Jobe AH, Bancalari E Bronchopulmonary dysplasia Am J Respir Crit Care Med 2001;163(7):1723-1729 108 Collaco JM, McGrath-Morrow SA Respiratory phenotypes for preterm infants, children, and adults: Bronchopulmonary dysplasia and more Ann Am Thorac Soc 2018;15(5):530-538 109 Higgins RD, Jobe AH, Koso-Thomas M, et al Bronchopulmonary dysplasia: Executive summary of a workshop J Pediatr 2018;197: 300-308 110 Steinhorn R, Davis JM, Gopel W, et al Chronic pulmonary insufficiency of prematurity: developing optimal endpoints for drug development J Pediatr 2017;191:15-21 111 Ahlfeld SK, Conway SJ Aberrant signaling pathways of the lung mesenchyme and their contributions to the pathogenesis of bronchopulmonary dysplasia Birth Defects Res A Clin Mol Teratol 2012;94(1):3-15 112 Jobe AH Mechanisms of lung injury and bronchopulmonary dysplasia Am J Perinatol 2016;33(11):1076-1078 113 Shahzad T, Radajewski S, Chao CM, et al Pathogenesis of bronchopulmonary dysplasia: when inflammation meets organ development Mol Cell Pediatr 2016;3(1):23 114 Laughon MM, Langer JC, Bose CL, et al Prediction of bronchopulmonary dysplasia by postnatal age in extremely premature infants Am J Respir Crit Care Med 2011;183(12):1715-1722 115 Wai KC, Kohn MA, Ballard RA, et al Early cumulative supplemental oxygen predicts bronchopulmonary dysplasia in high risk extremely low gestational age newborns J Pediatr 2016;177:97102 e102 116 Fairchild KD, Nagraj VP, Sullivan BA, et al Oxygen desaturations in the early neonatal period predict development of bronchopulmonary dysplasia Pediatr Res 2019;85(7):987-993 117 Raffay TM, Dylag AM, Sattar A, et al Neonatal intermittent hypoxemia events are associated with diagnosis of bronchopulmonary dysplasia at 36 weeks postmenstrual age Pediatr Res 2019;85(3): 318-323 118 Laughon M, Allred EN, Bose C, et al Patterns of respiratory disease during the first postnatal weeks in extremely premature infants Pediatrics 2009;123(4):1124-1131 119 Poindexter BB, Martin CR Impact of nutrition on bronchopulmonary dysplasia Clin Perinatol 2015;42(4):797-806 120 Khemani E, McElhinney DB, Rhein L, et al Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era Pediatrics 2007;120(6):1260-1269 121 Abman SH, Ivy DD, Archer SL, et al Executive summary of the American Heart Association and American Thoracic Society Joint Guidelines for pediatric pulmonary hypertension Am J Respir Crit Care Med 2016;194(7):898-906 122 Mandy G, Malkar M, Welty SE, et al Tracheostomy placement in infants with bronchopulmonary dysplasia: safety and outcomes Pediatr Pulmonol 2013;48(3):245-249 123 Cristea AI, Carroll AE, Davis SD, et al Outcomes of children with severe bronchopulmonary dysplasia who were ventilator dependent at home Pediatrics 2013;132(3):e727-734 124 Henningfeld JK, Maletta K, Ren B, et al Liberation from home mechanical ventilation and decannulation in children Pediatr Pulmonol 2016;51(8):838-849 125 Cheong JLY, Doyle LW An update on pulmonary and neurodevelopmental outcomes of bronchopulmonary dysplasia Semin Perinatol 2018;42(7):478-484 126 Ralser E, Mueller W, Haberland C, et al Rehospitalization in the first years of life in children born preterm Acta Paediatr 2012;101(1):e1-5 127 Been JV, Lugtenberg MJ, Smets E, et al Preterm birth and childhood wheezing disorders: a systematic review and meta-analysis PLoS Med 2014;11(1):e1001596 128 Fakhoury KF, Sellers C, Smith EO, et al Serial measurements of lung function in a cohort of young children with bronchopulmonary dysplasia Pediatrics 2010;125(6):e1441-1447 129 Narayanan M, Beardsmore CS, Owers-Bradley J, et al Catch-up alveolarization in ex-preterm children: evidence from (3)He magnetic resonance Am J Respir Crit Care Med 2013;187(10):11041109 130 Doyle LW, Adams AM, Robertson C, et al Increasing airway obstruction from to 18 years in extremely preterm/low-birthweight survivors born in the surfactant era Thorax 2017;72(8):712719 131 Um-Bergstrom P, Hallberg J, Thunqvist P, et al Lung function development after preterm birth in relation to severity of Bronchopulmonary dysplasia BMC Pulm Med 2017;17(1):97 132 Vollsaeter M, Roksund OD, Eide GE, et al Lung function after preterm birth: development from mid-childhood to adulthood Thorax 2013;68(8):767-776 133 Caskey S, Gough A, Rowan S, et al Structural and functional lung impairment in adult survivors of bronchopulmonary dysplasia Ann Am Thorac Soc 2016;13(8):1262-1270 134 Bahadue FL, Soll R Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome Cochrane Database Syst Rev 2012;11:CD001456 135 Klingenberg C, Wheeler KI, McCallion N, et al Volume-targeted versus pressure-limited ventilation in neonates Cochrane Database Syst Rev 2017;10:CD003666 e4 136 Araki S, Kato S, Namba F, et al Vitamin A to prevent bronchopulmonary dysplasia in extremely low birth weight infants: a systematic review and meta-analysis PLoS One 2018;13(11):e0207730 137 Nair V, Loganathan P, Soraisham AS Azithromycin and other macrolides for prevention of bronchopulmonary dysplasia: a systematic review and meta-analysis Neonatology 2014;106(4): 337-347 138 Watterberg KL, American Academy of Pediatrics, Committee on Fetus and Newborn Policy statement-postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia Pediatrics 2010;126(4):800-808 139 Doyle LW, Davis PG, Morley CJ, et al Low-dose dexamethasone facilitates extubation among chronically ventilator-dependent infants: a multicenter, international, randomized, controlled trial Pediatrics 2006;117(1):75-83 140 Baud O, Maury L, Lebail F, et al Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebocontrolled, multicentre, randomised trial Lancet 2016;387(10030): 1827-1836 141 Renault A, Patkai J, Dassieu G, et al Hydrocortisone use in ventilated extremely preterm infants decreased bronchopulmonary dysplasia with no effects on neurodevelopment after two years Acta Paediatr 2016;105(9):1047-1055 142 Bassler D Inhalation or instillation of steroids for the prevention of bronchopulmonary dysplasia Neonatology 2015;107(4): 358-359 143 Shah VS, Ohlsson A, Halliday HL, et al Early administration of inhaled corticosteroids for preventing chronic lung disease in very low birth weight preterm neonates Cochrane Database Syst Rev 2017;1:CD001969 144 Doyle LW, Halliday HL, Ehrenkranz RA, et al An update on the impact of postnatal systemic corticosteroids on mortality and cerebral palsy in preterm infants: effect modification by risk of bronchopulmonary dysplasia J Pediatr 2014;165(6):1258-1260 145 Fawke J, Lum S, Kirkby J, et al Lung function and respiratory symptoms at 11 years in children born extremely preterm: the EPICure study Am J Respir Crit Care Med 2010;182(2):237-245 146 Di Fiore JM, Dylag AM, Honomichl RD, et al Early inspired oxygen and intermittent hypoxemic events in extremely premature infants are associated with asthma medication use at years of age J Perinatol 2019;39(2):203-211 147 Clouse BJ, Jadcherla SR, Slaughter JL Systematic review of inhaled bronchodilator and corticosteroid therapies in infants with bronchopulmonary dysplasia: implications and future directions PLoS One 2016;11(2):e0148188 148 Chang YS, Ahn SY, Yoo HS, et al Mesenchymal stem cells for bronchopulmonary dysplasia: phase dose-escalation clinical trial J Pediatr 2014;164(5):966-972 149 Lapcharoensap W, Kan P, Powers RJ, et al The relationship of nosocomial infection reduction to changes in neonatal intensive care unit rates of bronchopulmonary dysplasia J Pediatr 2017;180: 105-109 150 Raffay TM, Martin RJ, Reynolds JD Can nitric oxide-based therapy prevent bronchopulmonary dysplasia? Clin Perinatol 2012;39(3):613-638 151 Raffay TM, Dylag AM, Di Fiore JM, et al S-nitrosoglutathione attenuates airway hyperresponsiveness in murine bronchopulmonary dysplasia Mol Pharmacol 2016;90(4):418-426 152 Gien J, Kinsella J, Thrasher J, et al Retrospective analysis of an interdisciplinary ventilator care program intervention on survival of infants with ventilator-dependent bronchopulmonary dysplasia Am J Perinatol 2017;34(2):155-163 153 Mullowney T, Manson D, Kim R, et al Primary ciliary dyskinesia and neonatal respiratory distress Pediatrics 2014;134(6):11601166 154 Davis SD, Ferkol TW, Rosenfeld M, et al Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype Am J Respir Crit Care Med 2015;191(3):316-324 155 Shapiro AJ, Zariwala MA, Ferkol T, et al Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review Pediatr Pulmonol 2016;51(2):115-132 156 Shapiro AJ, Davis SD, Polineni D, et al Diagnosis of primary ciliary dyskinesia An official American Thoracic Society Clinical Practice Guideline Am J Respir Crit Care Med 2018;197(12): e24-e39 157 Khalid F, Hannah WB, Gaston BM Rapid advances in primary ciliary dyskinesia research A brief update for pulmonologists (editorial) Am J Respir Crit Care Med 2019;199:136-138 e5 Abstract: Neonatal respiratory distress is a manifestation of diverse pathophysiologic conditions As this problem is typically associated with prematurity, disorders of the fetal-to-neonatal transition figure prominently in this review Furthermore, neonatal respiratory disorders and their management have the potential for longer-term morbidity into childhood and beyond In the term infant, the etiologies for neonatal respiratory distress are broader, encompassing congenital malformations and even nonrespiratory systemic conditions that manifest as pulmonary issues Key Words: tachypnea, apnea, interstitium, pulmonary air leak, mechanical ventilation, pulmonary hemorrhage 52 Pneumonitis and Interstitial Disease DAIVA PARAKININKAS PEARLS • Most pediatric pulmonary parenchymal disease occurs as a result of an infectious agent • Clinical evaluation for parenchymal lung disease in the pediatric patient should include a search for symptoms and signs associated with pulmonary disease, such as difficulty with feeding, exercise intolerance, chest pain, cough, tachypnea, dyspnea, cyanosis, orthopnea, clubbing of the nail beds, weight loss, and lethargy • Factors predisposing a child to bacterial pneumonia include having numerous siblings, smoke exposure, preterm delivery, living in an urban environment, poor socioeconomic status, presence of an airway foreign body, impaired immune response, congenital and anatomic lung defects, abnormalities of the tracheobronchial tree, cystic fibrosis, and congestive heart failure • Viral agents are the leading cause of lower respiratory tract infection in infants and children • Three major clinical syndromes are associated with lower respiratory tract viral illnesses: (1) bronchitis, (2) bronchiolitis, and (3) pneumonia • Fungal infections are important in the differential diagnosis of pulmonary infections, particularly in children whose immunity is compromised and in healthy children who are exposed to pathogens in a particular geographic or environmental setting • Three forms of disease patterns in pneumocystosis are (1) childhood/ adult, (2) infantile, and (3) chronic fibrosing, the last observed in some patients infected with the human immunodeficiency virus • Chemical pneumonitis and/or pneumonia may be acquired by (1) aspiration, (2) inhalation, (3) ingestion, or (4) injection • Pulmonary hemorrhage is a potentially life-threatening event that can occur at any age Clinical presentation varies from massive fatal hemoptysis to silent bleeding with respiratory distress and anemia Pneumonitis, or inflammation of the lung parenchyma, is perhaps the most common cause of life-threatening lower respiratory tract disease in pediatric patients Although pneumonitis may result from noninfectious processes (Box 52.1), most pediatric pulmonary parenchymal disease occurs as the result of an infectious agent Pneumonitis may involve the pleura, interstitium, and airways; pneumonia, by definition, must include alveolar consolidation Whereas early parenchymal lung injury is associated with increased cellularity with minimal fibrosis, advanced disease is characterized by extensive fibrosis and destruction of gas-exchange units Physiologic changes may include the following: low lung volumes, diminished lung compliance, impaired gas exchange, and airflow limitation This chapter addresses the principal potential causes of pediatric pulmonary parenchymal disease, including alveolar and interstitial disorders cells Other agents may injure the lung indirectly by one or more of the following processes: Generation of toxic radicals Recruitment of inflammatory cells (e.g., neutrophils) Activation of complement and/or release of chemotactic factors If these processes go unchecked, alterations may occur in the lung parenchyma and connective tissues, leading to end-stage fibrosis This condition is characterized by destruction of gasexchange units and airways and the development of parenchymal cystic lesions Pathogenesis Regardless of the cause, pneumonitis often follows a common pathogenesis The initial parenchymal injury can result from mechanisms that directly damage the endothelium or epithelial Pathophysiology Changes in lung volumes in pulmonary parenchymal disease depend primarily on the intensity of the alveolitis and stage of the disease process Acute severe pneumonitis with intense alveolitis is characterized by moderate to severe reduction in both vital capacity (VC) and total lung capacity It is also associated with a reduction in pulmonary compliance In the early stages, patients with chronic interstitial diseases involving the lung parenchyma often have normal VC and total lung capacity Subsequent reduction in 585 ... diverse pathophysiologic conditions As this problem is typically associated with prematurity, disorders of the fetal-to-neonatal transition figure prominently in this review Furthermore, neonatal... dysplasia? Clin Perinatol 2012;39(3):613-638 151 Raffay TM, Dylag AM, Di Fiore JM, et al S-nitrosoglutathione attenuates airway hyperresponsiveness in murine bronchopulmonary dysplasia Mol Pharmacol... Pediatr Surg 2002;37:331-338 94 Murphy JJ, Blair GK, Fraser GC, et al Rhabdomyosarcoma arising within congenital pulmonary cysts: report of three cases J Pediatr Surg 1992;27:1364-1367 95 Granata