急性和慢性肺损伤的模式及病因：基于非临床性实验证据的剖析

Matthias C. H&#252; tten; Boris W. Kramer

doi:10.7499/j.issn.1008-8830.2014.05.002

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中国当代儿科杂志 ›› 2014, Vol. 16 ›› Issue (5) : 448-459. DOI: 10.7499/j.issn.1008-8830.2014.05.002

国外儿科动态

急性和慢性肺损伤的模式及病因：基于非临床性实验证据的剖析

Matthias C. Hütten^1,2, Boris W. Kramer²

作者信息 +

Patterns and etiology of acute and chronic lung injury：insights from experimental evidence

Matthias C. Hütten^1,2, Boris W. Kramer²

Author information +

文章历史 +

摘要

满足最基本需求的肺功能是早产儿存活的先决条件。早产儿肺结构和功能欠成熟，常常伴发呼吸窘迫综合征（RDS）。除结构不成熟之外，早产儿肺组织还易因出生前后各种不利状况及因素而受损，进而防碍生后肺部的正常发育，促发非成熟性慢性肺部病变，导致支气管肺发育不良（BPD）。该文将以由炎症变化而引发并与炎症变化密切相关的肺损伤为重点，全面综述用以探讨早产儿肺部炎症反应机制的各种实验模型，这其中包括用来研究绒毛膜羊膜炎发病机制的模型。

Abstract

Adequate pulmonary function is pivotal for preterm infants. Besides being structurally immature, the preterm lung is susceptible to injury resulting from different prenatal conditions and postnatal insults. Lung injury might result in impaired postnatal lung development, contributing to chronic lung disease of prematurity, bronchopulmonary dysplasia (BPD). This review focuses on lung injury mediated by and related to inflammatory changes in the lung. We give an overview on experimental models which have helped to elucidate mechanisms of pulmonary inflammation in prematurity. We describe experimental data linking acute and chronic chorioamnionitis with intrapulmonary inflammation, lung maturation and surfactant production in various animal models. In addition, experimental data has shown that fetal inflammatory response is modulated by the fetus himself. Experimental data has therefore helped to understand differential effects on lung function and lung maturation exerted by maternal administration of potentially anti-inflammatory substances like glucocorticosteroids (GCS). New approaches of modulation of pulmonary inflammation/injury caused by postnatal interventions during resuscitation and mechanical ventilation have been studied in animal models. Postnatal therapeutic interventions with widely used drugs like oxygen, steroids, surfactant, caffeine and vitamin A have been experimentally and mechanistically assessed regarding their effect on pulmonary inflammation and lung injury. Carefully designed experiments will help to elucidate the complex interaction between lung injury, lung inflammation, repair and altered lung development, and will help to establish a link between lung alterations originating in this early period of life and long-term adverse respiratory effects.

导出引用

Matthias C. Hütten, Boris W. Kramer. 急性和慢性肺损伤的模式及病因：基于非临床性实验证据的剖析[J]. 中国当代儿科杂志. 2014, 16(5): 448-459 https://doi.org/10.7499/j.issn.1008-8830.2014.05.002

Matthias C. Hütten, Boris W. Kramer. Patterns and etiology of acute and chronic lung injury：insights from experimental evidence[J]. Chinese Journal of Contemporary Pediatrics. 2014, 16(5): 448-459 https://doi.org/10.7499/j.issn.1008-8830.2014.05.002

参考文献

[1] Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery[J]. N Engl J Med, 2000, 342(20): 1500-1507.
[2] Gantert M, Been JV, Gavilanes AW, et al. Chorioamnionitis: a multiorgan disease of the fetus? [J]. J Perinatol, 2010, 30 (Suppl): S21-S30.
[3] Lahra MM, Beeby PJ, Jeffery HE. Maternal versus fetal inflammation and respiratory distress syndrome: a 10-year hospital cohort study[J]. Arch Dis Child Fetal Neonatal Ed, 2009, 94(1): F13-16.
[4] Been JV, Zimmermann LJ. Histological chorioamnionitis and respiratory outcome in preterm infants[J]. Arch Dis Child Fetal Neonatal Ed, 2009, 94(3): F218-225.
[5] Watterberg KL, Demers LM, Scott SM, et al. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops[J]. Pediatrics, 1996, 97(2): 210-215.
[6] Jobe AH. What is RDS in 2012? [J]. Early Hum Dev, 2012, 88 (Suppl 2): S42-S44.
[7] Jobe AH. What is BPD in 2012 and what will BPD become? [J]. Early Hum Dev, 2012, 88 (Suppl 2): S27-S28.
[8] Van Marter LJ, Dammann O, Allred EN, et al. Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants[J]. J Pediatr, 2002, 140(2): 171-176.
[9] Kunzmann S, Collins JJP, Kuypers E, et al. Thrown off balance: the effect of antenatal inflammation on the developing lung and immune system[J]. Am J Obstet Gynecol, 2013, 208(6): 429-437.
[10] Bry K, Lappalainen U, Hallman M. Intraamniotic interleukin-1 accelerates surfactant protein synthesis in fetal rabbits and improves lung stability after premature birth[J]. J Clin Invest, 1997, 99(12): 2992-2999.
[11] Willet KE, Kramer BW, Kallapur SG, et al. Intra-amniotic injection of IL-1 induces inflammation and maturation in fetal sheep lung[J]. Am J Physiol Lung Cell Mol Physiol, 2002, 282(3): L411-420.
[12] Sosenko IR, Kallapur SG, Nitsos I, et al. IL-1 alpha causes lung inflammation and maturation by direct effects on preterm fetal lamb lungs[J]. Pediatr Res, 2006 60(3): 294-298.
[13] Glumoff V, Vayrynen O, Kangas T, et al. Degree of lung maturity determines the direction of the interleukin-1- induced effect on the expression of surfactant proteins[J]. Am J Respir Cell Mol Biol, 2000, 22(3): 280-228.
[14] Kallapur SG, Nitsos I, Moss TJ, et al. IL-1 mediates pulmonary and systemic inflammatory responses to chorioamnionitis induced by lipopolysaccharide[J]. Am J Respir Crit Care Med, 2009, 179(10): 955-961.
[15] Kramer BW, Moss TJ, Willet KE, et al. Dose and time response after intraamniotic endotoxin in preterm lambs[J]. Am J Respir Crit Care Med, 2001, 164(6): 982-988.
[16] Kallapur SG, Willet KE, Jobe AH, et al. Intra-amniotic endotoxin: chorioamnionitis precedes lung maturation in preterm lambs[J]. Am J Physiol Lung Cell Mol Physiol, 2001, 280(3): L527-L536.
[17] Kallapur SG, Kramer BW, Jobe AH. Ureaplasma and BPD[J]. Semin Perinatol, 2013, 37(2): 94-101.
[18] DiGiulio DB, Romero R, Amogan HP, et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation[J]. PLoS One, 2008, 3(8): e3056.
[19] Kotecha S, Hodge R, Schaber JA, et al. Pulmonary Ureaplasma urealyticum is associated with the development of acute lung inflammation and chronic lung disease in preterm infants[J]. Pediatr Res, 2004, 55(1): 61-68.
[20] Collins JJ, Kallapur SG, Knox CL, et al. Inflammation in fetal sheep from intra-amniotic injection of Ureaplasma parvum[J]. Am J Physiol Lung Cell Mol Physiol, 2010, 299(6): L852-L860.
[21] Polglase GR, Dalton RG, Nitsos I, et al. Pulmonary vascular and alveolar development in preterm lambs chronically colonized with Ureaplasma parvum[J]. Am J Physiol Lung Cell Mol Physiol, 2010, 299(2): L232-L241.
[22] Moss TJ, Knox CL, Kallapur SG, et al. Experimental amniotic fluid infection in sheep: effects of Ureaplasma parvum serovars 3 and 6 on preterm or term fetal sheep[J]. Am J Obstet Gynecol, 2008, 198(1): 122 e1-8.
[23] Moss TJ, Newnham JP, Willett KE, et al. Early gestational intra-amniotic endotoxin: lung function, surfactant, and morphometry[J]. Am J Respir Crit Care Med, 2002, 165(6): 805-811.
[24] Kramer BW, Kallapur S, Newnham J, et al. Prenatal inflammation and lung development[J]. Semin Fetal Neonatal Med, 2009, 14(1): 2-7.
[25] Kramer BW, Jobe AH. The clever fetus: responding to inflammation to minimize lung injury[J]. Biol Neonate, 2005, 88(3): 202-207.
[26] Kallapur SG, Nitsos I, Moss TJ, et al. Chronic endotoxin exposure does not cause sustained structural abnormalities in the fetal sheep lungs[J]. Am J Physiol Lung Cell Mol Physiol, 2005, 288(5): L966-L974.
[27] Kallapur SG, Jobe AH, Ball MK, et al. Pulmonary and systemic endotoxin tolerance in preterm fetal sheep exposed to chorioamnionitis[J]. J Immunol, 2007, 179(12): 8491-8499.
[28] Kramer BW. Chorioamnionitis-new ideas from experimental models[J]. Neonatology, 2011, 99(4): 320-325.
[29] Kramer BW, Kallapur SG, Moss TJ, et al. Intra-amniotic LPS modulation of TLR signaling in lung and blood monocytes of fetal sheep[J]. Innate Immun, 2009, 15(2): 101-107.
[30] Kallapur SG, Kramer BW, Knox CL, et al. Chronic fetal exposure to Ureaplasma parvum suppresses innate immune responses in sheep[J]. J Immunol, 2011, 187(5): 2688-2695.
[31] Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes[J]. Jama, 1995, 273(5): 413-418.
[32] Willet KE, Jobe AH, Ikegami M. Antenatal endotoxin and glucocorticoid effects on lung morphometry in preterm lambs[J]. Pediatr Res, 2000, 48(6): 782-788.
[33] Jobe AH, Newnham JP, Willet KE, et al. Endotoxin-induced lung maturation in preterm lambs is not mediated by cortisol[J]. Am J Respir Crit Care Med, 2000, 162(5): 1656-1661.
[34] Goldenberg RL, Andrews WW, Faye-Petersen OM, et al. The Alabama preterm birth study: corticosteroids and neonatal outcomes in 23- to 32-week newborns with various markers of intrauterine infection[J]. Am J Obstet Gynecol, 2006, 195(4): 1020-1024.
[35] Been JV, Degraeuwe PL, Kramer BW, et al. Antenatal steroids and neonatal outcome after chorioamnionitis: a meta-analysis[J]. Bjog, 2011, 118(2): 113-122.
[36] Kallapur SG, Kramer BW, Moss TJ, et al. Maternal glucocorticoids increase endotoxin-induced lung inflammation in preterm lambs[J]. Am J Physiol Lung Cell Mol Physiol, 2003, 284(4): L633-L642.
[37] Kuypers E, Collins JJ, Kramer BW, et al. Intra-amniotic LPS and antenatal betamethasone: inflammation and maturation in preterm lamb lungs[J]. Am J Physiol Lung Cell Mol Physiol, 2012, 302(4): L380-L389.
[38] Vayrynen O, Glumoff V, Hallman M. Inflammatory and anti-inflammatory responsiveness of surfactant proteins in fetal and neonatal rabbit lung[J]. Pediatr Res, 2004, 55(1): 55-60.
[39] Bartram U, Speer CP. The role of transforming growth factor beta in lung development and disease[J]. Chest, 2004, 125(2): 754-765.
[40] Kotecha S, Wangoo A, Silverman M, et al. Increase in the concentration of transforming growth factor beta-1 in bronchoalveolar lavage fluid before development of chronic lung disease of prematurity[J]. J Pediatr, 1996, 128(4): 464-469.
[41] Kunzmann S, Speer CP, Jobe AH, et al. Antenatal inflammation induced TGF-beta1 but suppressed CTGF in preterm lungs[J]. Am J Physiol Lung Cell Mol Physiol, 2007, 292(1): L223-L231.
[42] Lecart C, Cayabyab R, Buckley S, et al. Bioactive transforming growth factor-beta in the lungs of extremely low birthweight neonates predicts the need for home oxygen supplementation[J]. Biol Neonate, 2000, 77(4): 217-223.
[43] Collins JJ, Kunzmann S, Kuypers E, et al. Antenatal glucocorticoids counteract LPS changes in TGF-beta pathway and caveolin-1 in ovine fetal lung[J]. Am J Physiol Lung Cell Mol Physiol, 2013, 304(6): L438-L444.
[44] Collins JJ, Kuypers E, Nitsos I, et al. LPS-induced chorioamnionitis and antenatal corticosteroids modulate Shh signaling in the ovine fetal lung[J]. Am J Physiol Lung Cell Mol Physiol, 2012, 303(9): L778-L787.
[45] Sweet DG, Huggett MT, Warner JA, et al. Maternal betamethasone and chorioamnionitis induce different collagenases during lung maturation in fetal sheep[J]. Neonatology, 2008, 94(2): 79-86.
[46] Bjorklund LJ, Ingimarsson J, Curstedt T, et al. Manual ventilation with a few large breaths at birth compromises the therapeutic effect of subsequent surfactant replacement in immature lambs[J]. Pediatr Res, 1997, 42(3):348-355.
[47] te Pas AB, Siew M, Wallace MJ, et al. Effect of sustained inflation length on establishing functional residual capacity at birth in ventilated premature rabbits[J]. Pediatr Res, 2009, 66(3): 295-300.
[48] Klingenberg C, Sobotka KS, Ong T, et al. Effect of sustained inflation duration; resuscitation of near-term asphyxiated lambs[J]. Arch Dis Child Fetal Neonatal Ed, 2013, 98(3): F222-F227.
[49] Hillman NH, Kemp MW, Noble PB, et al. Sustained Inflation at birth did not protect preterm fetal sheep from lung injury[J]. Am J Physiol Lung Cell Mol Physiol, 2013, 305(6): L446-L453.
[50] Michna J, Jobe AH, Ikegami M. Positive end-expiratory pressure preserves surfactant function in preterm lambs[J]. Am J Respir Crit Care Med, 1999, 160(2): 634-649.
[51] Naik AS, Kallapur SG, Bachurski CJ, et al. Effects of ventilation with different positive end-expiratory pressures on cytokine expression in the preterm lamb lung[J]. Am J Respir Crit Care Med, 2001, 164(3): 494-498.
[52] Hillman NH, Kallapur SG, Pillow JJ, et al. Airway injury from initiating ventilation in preterm sheep[J]. Pediatr Res, 2010, 67(1): 60-65.
[53] Fuchs H, Mendler MR, Scharnbeck D, et al. Very low tidal volume ventilation with associated hypercapnia--effects on lung injury in a model for acute respiratory distress syndrome[J]. PLoS One, 2011, 6(8): e23816.
[54] Yoder BA, Siler-Khodr T, Winter VT, et al. High-frequency oscillatory ventilation: effects on lung function, mechanics, and airway cytokines in the immature baboon model for neonatal chronic lung disease[J]. Am J Respir Crit Care Med, 2000, 162(5): 1867-1876.
[55] Cools F, Askie LM, Offringa M, et al. Elective high-frequency oscillatory versus conventional ventilation in preterm infants: a systematic review and meta-analysis of individual patients' data[J]. Lancet, 2010, 375(9731): 2082-2091.
[56] Gopel W, Kribs A, Ziegler A, et al. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial[J]. Lancet, 2011, 378(9803): 1627-1634.
[57] Gittermann MK, Fusch C, Gittermann AR, et al. Early nasal continuous positive airway pressure treatment reduces the need for intubation in very low birth weight infants[J]. Eur J Pediatr, 1997, 156(5): 384-388.
[58] Jobe AH, Kramer BW, Moss TJ, et al. Decreased indicators of lung injury with continuous positive expiratory pressure in preterm lambs[J]. Pediatr Res, 2002, 52(3): 387-392.
[59] Thomson MA, Yoder BA, Winter VT, et al. Treatment of immature baboons for 28 days with early nasal continuous positive airway pressure[J]. Am J Respir Crit Care Med, 2004, 169(9): 1054-1062.
[60] Bland RD, Xu L, Ertsey R, et al. Dysregulation of pulmonary elastin synthesis and assembly in preterm lambs with chronic lung disease[J]. Am J Physiol Lung Cell Mol Physiol, 2007, 292(6): L1370-L1384.
[61] Tremblay L, Valenza F, Ribeiro SP, et al. Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model[J]. J Clin Invest, 1997, 99(5): 944-952.
[62] Ricard JD, Dreyfuss D, Saumon G. Production of inflammatory cytokines in ventilator-induced lung injury: a reappraisal[J]. Am J Respir Crit Care Med, 2001, 163(5): 1176-1180.
[63] Kramer BW, Kramer S, Ikegami M, et al. Injury, inflammation, and remodeling in fetal sheep lung after intra-amniotic endotoxin[J]. Am J Physiol Lung Cell Mol Physiol, 2002, 283(2): L452-L459.
[64] Polglase GR, Hillman NH, Ball MK, et al. Lung and systemic inflammation in preterm lambs on continuous positive airway pressure or conventional ventilation[J]. Pediatr Res, 2009, 65(1): 67-71.
[65] Polglase GR, Hillman NH, Pillow JJ, et al. Ventilation-mediated injury after preterm delivery of Ureaplasma parvum colonized fetal lambs[J]. Pediatr Res, 2010, 67(6): 630-635.
[66] Hillman NH, Pillow JJ, Ball MK, et al. Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep[J]. Respir Res, 2009, 10: 124.
[67] Kramer BW, Ladenburger A, Kunzmann S, et al. Intravenous lipopolysaccharide-induced pulmonary maturation and structural changes in fetal sheep[J]. Am J Obstet Gynecol, 2009, 200(2): 195 e1-10.
[68] Gisslen T, Hillman NH, Musk GC, et al. Repeated exposure to intra-amniotic LPS partially protects against adverse effects of intravenous LPS in preterm lambs[J]. Innate Immun, 2013, 20(2): 214-224.
[69] Carlo WA, Finer NN, Walsh MC, et al. Target ranges of oxygen saturation in extremely preterm infants[J]. N Engl J Med, 2010, 362(21): 1959-1969.
[70] Stenson B, Brocklehurst P, Tarnow-Mordi W. Increased 36-week survival with high oxygen saturation target in extremely preterm infants[J]. N Engl J Med, 2011, 364(17): 1680-1682.
[71] Supplemental Therapeutic Oxygen for Prethreshold Retinopathy Of Prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes[J]. Pediatrics, 2000, 105(2): 295-310.
[72] Van Marter LJ, Allred EN, Pagano M, et al. Do clinical markers of barotrauma and oxygen toxicity explain interhospital variation in rates of chronic lung disease? The Neonatology Committee for the Developmental Network[J]. Pediatrics, 2000, 105(6): 1194-1201.
[73] Saugstad OD. Update on oxygen radical disease in neonatology[J]. Curr Opin Obstet Gynecol, 2001, 13(2): 147-153.
[74] Rogers S, Witz G, Anwar M, et al. Antioxidant capacity and oxygen radical diseases in the preterm newborn[J]. Arch Pediatr Adolesc Med, 2000, 154(6): 544-548.
[75] Warner BB, Stuart LA, Papes RA, et al. Functional and pathological effects of prolonged hyperoxia in neonatal mice[J]. Am J Physiol, 1998, 275(1 Pt 1): L110-L117.
[76] Rozycki HJ, Comber PG, Huff TF. Cytokines and oxygen radicals after hyperoxia in preterm and term alveolar macrophages[J]. Am J Physiol Lung Cell Mol Physiol, 2002, 282(6): L1222-L1228.
[77] Weinberger B, Nisar S, Anwar M, Ostfeld B, Hegyi T. Lipid peroxidation in cord blood and neonatal outcome[J]. Pediatr Int, 2006, 48(5): 479-483.
[78] Cheah FC, Jobe AH, Moss TJ, et al. Oxidative stress in fetal lambs exposed to intra-amniotic endotoxin in a chorioamnionitis model[J]. Pediatr Res, 2008, 63(3): 274-279.
[79] Sosenko IR, Jobe AH. Intraamniotic endotoxin increases lung antioxidant enzyme activity in preterm lambs[J]. Pediatr Res, 2003, 53(4): 679-683.
[80] Been JV, Rours IG, Kornelisse RF, et al. Chorioamnionitis alters the response to surfactant in preterm infants[J]. J Pediatr, 2010, 156(1): 10-5 e1.
[81] Seehase M, Collins JJ, Kuypers E, et al. New surfactant with SP-B and C analogs gives survival benefit after inactivation in preterm lambs[J]. PLoS One, 2012, 7(10): e47631.
[82] Gille C, Spring B, Bernhard W, et al. Differential effect of surfactant and its saturated phosphatidylcholines on human blood macrophages[J]. J Lipid Res, 2007, 48(2): 307-317.
[83] Fehrholz M, Bersani I, Kramer BW, et al. Synergistic effect of caffeine and glucocorticoids on expression of surfactant protein B (SP-B) mRNA[J]. PLoS One, 2012, 7(12): e51575.
[84] Fehrholz M, Hutten M, Kramer BW, et al. Amplification of steroid-mediated SP-B expression by physiological levels of caffeine[J]. Am J Physiol Lung Cell Mol Physiol, 2014,306(1): L101-L109.
[85] Moreira A, Caskey M, Fonseca R, et al. Impact of providing vitamin A to the routine pulmonary care of extremely low birth weight infants[J]. J Matern Fetal Neona, 2012, 25(1): 84-88.
[86] Ozer EA, Kumral A, Ozer E, et al. Effect of retinoic acid on oxygen-induced lung injury in the newborn rat[J]. Pediatr Pulmonol, 2005, 39(1): 35-40.
[87] Pierce RA, Joyce B, Officer S, et al. Retinoids increase lung elastin expression but fail to alter morphology or angiogenesis genes in premature ventilated baboons[J]. Pediatr Res, 2007, 61(6): 703-709.
[88] Kramer BW, Albertine KH, Moss TJ, et al. All-trans retinoic acid and intra-amniotic endotoxin-mediated effects on fetal sheep lung[J]. Anat Rec (Hoboken), 2008, 291(10): 1271-1277.
[89] Eichenwald EC, Stark AR. Are postnatal steroids ever justified to treat severe bronchopulmonary dysplasia?[J]. Arch Dis Child Fetal Neonatal Ed, 2007, 92(5): F334- F337.
[90] Halliday HL, Ehrenkranz RA, Doyle LW. Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants[J]. Cochrane Database Syst Rev, 2009, (1):CD001146.
[91] Halliday HL, Ehrenkranz RA, Doyle LW. Late (>7 days) postnatal corticosteroids for chronic lung disease in preterm infants[J]. Cochrane Database Syst Rev, 2009(1):CD001145.
[92] Barrington KJ. The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs[J]. BMC Pediatr, 2001, 1:1.
[93] Watterberg KL, Shaffer ML, Mishefske MJ, et al. Growth and neurodevelopmental outcomes after early low-dose hydrocortisone treatment in extremely low birth weight infants[J]. Pediatrics, 2007, 120(1): 40-48.
[94] Lee HJ, Kim BI, Choi ES, et al. Effects of postnatal dexamethasone or hydrocortisone in a rat model of antenatal lipopolysaccharide and neonatal hyperoxia exposure[J]. J Korean Med Sci, 2012, 27(4): 395-401.
[95] Huang CC, Lin HR, Liang YC, et al. Effects of neonatal corticosteroid treatment on hippocampal synaptic function[J]. Pediatr Res, 2007, 62(3): 267-270.
[96] Onland W, Offringa M, Cools F, et al. Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial[J]. BMC Pediatr, 2011, 11:102.
[97] Fung ME, Thebaud B. Stem cell-based therapy for neonatal lung disease-it's in the juice[J]. Pediatr Res, 2014, 75(1-1): 2-7.
[98] Brostrom EB, Akre O, Katz-Salamon M, et al. Obstructive pulmonary disease in old age among individuals born preterm[J]. Eur J Epidemiol, 2013, 28(1): 79-85.
[99] Kumar R, Yu Y, Story RE, et al. Prematurity, chorioamnionitis, and the development of recurrent wheezing: a prospective birth cohort study[J]. J Allergy Clin Immunol, 2008, 121(4): 878-884.
[100] Wong PM, Lees AN, Louw J, et al. Emphysema in young adult survivors of moderate-to-severe bronchopulmonary dysplasia[J]. Eur Respir J, 2008, 32(2): 321-328.
[101] Larsen PS, Kamper-Jorgensen M, Adamson A, et al. Pregnancy and birth cohort resources in europe: a large opportunity for aetiological child health research[J]. Paediatr Perinat Epidemiol, 2013, 27(4): 393-414.