Prematurity and respiratory outcomes program (PROP): study protocol of a prospective multicenter study of respiratory outcomes of preterm infants in the United States

BMC Pediatrics

Aaron Hamvas¹  Lynn M Taussig^1,10  Pamela Shaw⁸  Clement Ren²  Howard Panitch⁷  Thomas J Mariani⁶  James Kemp¹  James M Greenberg³  Jonas H Ellenberg⁸  Stephanie D Davis⁴  Denise Cifelli⁸  Roberta A Ballard⁵  Nathalie L Maitre⁹  Gloria S Pryhuber² 

[1] Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA;Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA;Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA;Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA;Department of Pediatrics, University of California, San Francisco School of Medicine, San Francisco, CA, USA;Department of Pediatrics and Pediatric Molecular and Personalized Medicine Program, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA;Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA;Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;Monroe Carrell Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA;Department of Pediatrics, University of Colorado, Provost’s Office, University of Denver, Denver, CO, USA

关键词: Bronchopulmonary dysplasia;    Chronic lung disease;    Preterm;    Infant;    Prematurity;   

Others  :  1203860
DOI  :  10.1186/s12887-015-0346-3

 received in 2014-12-23, accepted in 2015-03-11,  发布年份 2015

【 摘 要 】

Background

With improved survival rates, short- and long-term respiratory complications of premature birth are increasing, adding significantly to financial and health burdens in the United States. In response, in May 2010, the National Institutes of Health (NIH) and the National Heart, Lung, and Blood Institute (NHLBI) funded a 5-year $18.5 million research initiative to ultimately improve strategies for managing the respiratory complications of preterm and low birth weight infants. Using a collaborative, multi-disciplinary structure, the resulting Prematurity and Respiratory Outcomes Program (PROP) seeks to understand factors that correlate with future risk for respiratory morbidity.

Methods/Design

The PROP is an observational prospective cohort study performed by a consortium of six clinical centers (incorporating tertiary neonatal intensive care units [NICU] at 13 sites) and a data-coordinating center working in collaboration with the NHLBI. Each clinical center contributes subjects to the study, enrolling infants with gestational ages 23 0/7 to 28 6/7 weeks with an anticipated target of 750 survivors at 36 weeks post-menstrual age. In addition, each center brings specific areas of scientific focus to the Program. The primary study hypothesis is that in survivors of extreme prematurity specific biologic, physiologic and clinical data predicts respiratory morbidity between discharge and 1 year corrected age. Analytic statistical methodology includes model-based and non-model-based analyses, descriptive analyses and generalized linear mixed models.

Discussion

PROP incorporates aspects of NICU care to develop objective biomarkers and outcome measures of respiratory morbidity in the <29 week gestation population beyond just the NICU hospitalization, thereby leading to novel understanding of the nature and natural history of neonatal lung disease and of potential mechanistic and therapeutic targets in at-risk subjects.

Trial registration

Clinical Trials.gov NCT01435187 webcite.

【 授权许可】

   
2015 Pryhuber et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]Maitre NL, Ballard RA, Ellenberg JH, Davis SD, Greenberg JM, Hamvas A, et al. Respiratory consequences of prematurity: evolution of a diagnosis and development of a comprehensive approach. J Perinatol. 2015; doi:10.1038/jp.2015.19 [Epub ahead of print].
• [2]Martinez FD, Morgan WJ, Wright AL, Holberg CJ, Taussig LM. Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. N Engl J Med. 1988; 319(17):1112-1117.
• [3]Martinez FD, Morgan WJ, Wright AL, Holberg C, Taussig LM. Initial airway function is a risk factor for recurrent wheezing respiratory illnesses during the first three years of life. Group Health Medical Associates. Am Rev Respir Dis. 1991; 143(2):312-316.
• [4]Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995; 332(3):133-138.
• [5]Taussig LM, Wright AL, Holberg CJ, Halonen M, Morgan WJ, Martinez FD. Tucson Children’s Respiratory Study: 1980 to present. J Allergy Clin Immunol. 2003; 111(4):661-675.
• [6]Wright AL, Holberg C, Martinez FD, Taussig LM. Relationship of parental smoking to wheezing and nonwheezing lower respiratory tract illnesses in infancy. Group Health Medical Associates. J Pediatr. 1991; 118(2):207-214.
• [7]Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG et al.. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med. 2010; 362(21):1970-1979.
• [8]Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG et al.. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med. 2010; 362(21):1959-1969.
• [9]Stevens TP, Finer NN, Carlo WA, Szilagyi PG, Phelps DL, Walsh MC et al.. Respiratory outcomes of the surfactant positive pressure and oximetry randomized trial (SUPPORT). J Pediatr. 2014; 165(2):240-249.
• [10]Kleinman L, Rothman M, Strauss R, Orenstein SR, Nelson S, Vandenplas Y et al.. The infant gastroesophageal reflux questionnaire revised: development and validation as an evaluative instrument. Clin Gastroenterol Hepatol. 2006; 4(5):588-596.
• [11]Bose CL, Dammann CE, Laughon MM. Bronchopulmonary dysplasia and inflammatory biomarkers in the premature neonate. Arch Dis Child Fetal Neonatal Ed. 2008; 93(6):F455-F461.
• [12]Allen JL, Wolfson MR, McDowell K, Shaffer TH. Thoracoabdominal asynchrony in infants with airflow obstruction. Am RevRespir Dis. 1990; 141(2):337-342.
• [13]Håland G, Carlsen KCL, Sandvik L, Devulapalli CS, Munthe-Kaas MC, Pettersen M et al.. Reduced lung function at birth and the risk of asthma at 10 years of age. N Engl J Med. 2006; 355(16):1682-1689.
• [14]Deoras KS, Greenspan JS, Wolfson MR, Keklikian EN, Shaffer TH, Allen JL. Effects of inspiratory resistive loading on chest wall motion and ventilation: differences between preterm and full-term infants. Pediatr Res. 1992; 32(5):589-594.
• [15]Morris MJ, Lane DJ. Tidal expiratory flow patterns in airflow obstruction. Thorax. 1981; 36(2):135-142.
• [16]Palmer J, Allen J, Mayer O. Tidal breathing analysis. NeoReviews. 2004; 5:E186-E193.
• [17]Sackner MA, Watson H, Belsito AS, Feinerman D, Suarez M, Gonzalez G et al.. Calibration of respiratory inductive plethysmograph during natural breathing. J Appl Physiol. 1989; 66(1):410-420.
• [18]Warren RH, Horan SM, Robertson PK. Chest wall motion in preterm infants using respiratory inductive plethysmography. Eur Respir J. 1997; 10(10):2295-2300.
• [19]Tourneux P, Leke A, Kongolo G, Cardot V, Degrugilliers L, Chardon K et al.. Relationship between functional residual capacity and oxygen desaturation during short central apneic events during sleep in “late preterm” infants. Pediatr Res. 2008; 64(2):171-176.
• [20]Shennan AT, Dunn MS, Ohlsson A, Lennox K, Hoskins EM. Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics. 1988; 82(4):527-532.
• [21]Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001; 163(7):1723-1729.
• [22]Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA et al.. Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia. Pediatrics. 2005; 116(6):1353-1360.
• [23]Walsh MC, Wilson-Costello D, Zadell A, Newman N, Fanaroff A. Safety, reliability, and validity of a physiologic definition of bronchopulmonary dysplasia. J Perinatol. 2003; 23(6):451-456.
• [24]Walsh MC, Yao Q, Gettner P, Hale E, Collins M, Hensman A et al.. Impact of a physiologic definition on bronchopulmonary dysplasia rates. Pediatrics. 2004; 114(5):1305-1311.
• [25]Samuels MP. The effects of flight and altitude. Arch Dis Child. 2004; 89(5):448-455.
• [26]Managing passengers with respiratory disease planning air travel: British Thoracic Society recommendations. Thorax. 2002; 57(4):289-304.
• [27]Klassen TP, Sutcliffe T, Watters LK, Wells GA, Allen UD, Li MM. Dexamethasone in salbutamol-treated inpatients with acute bronchiolitis: a randomized, controlled trial. J Pediatr. 1997; 130(2):191-196.
• [28]Lowell DI, Lister G, Von Koss H, McCarthy P. Wheezing in infants: the response to epinephrine. Pediatrics. 1987; 79(6):939-945.
• [29]Schuh S, Coates AL, Binnie R, Allin T, Goia C, Corey M et al.. Efficacy of oral dexamethasone in outpatients with acute bronchiolitis. J Pediatr. 2002; 140(1):27-32.
• [30]Bueno Campana M, Olivares Ortiz J, Notario Munoz C, Ruperez Lucas M, Fernandez Rincon A, Patino Hernandez O et al.. High flow therapy versus hypertonic saline in bronchiolitis: randomised controlled trial. Arch Dis Child. 2014; 99(6):511-515.
• [31]McCallum GB, Morris PS, Wilson CC, Versteegh LA, Ward LM, Chatfield MD et al.. Severity scoring systems: are they internally valid, reliable and predictive of oxygen use in children with acute bronchiolitis? Pediatr Pulmonol. 2013; 48(8):797-803.
• [32]Hoo AF, Dezateux C, Henschen M, Costeloe K, Stocks J. Development of airway function in infancy after preterm delivery. J Pediatr. 2002; 141(5):652-658.
• [33]Friedrich L, Stein RT, Pitrez PM, Corso AL, Jones MH. Reduced lung function in healthy preterm infants in the first months of life. Am J Respir Crit Care Med. 2006; 173(4):442-447.
• [34]Bhandari A, Panitch HB. Pulmonary outcomes in bronchopulmonary dysplasia. Semin Perinatol. 2006; 30(4):219-226.
• [35]Robin B, Kim YJ, Huth J, Klocksieben J, Torres M, Tepper RS et al.. Pulmonary function in bronchopulmonary dysplasia. Pediatr Pulmonol. 2004; 37(3):236-242.
• [36]ATS/ERS statement: raised volume forced expirations in infants: guidelines for current practice. Am J Respir Crit Care Med. 2005; 172(11):1463-1471.
• [37]Goldstein AB, Castile RG, Davis SD, Filbrun DA, Flucke RL, McCoy KS et al.. Bronchodilator responsiveness in normal infants and young children. Am J Respir Crit Care Med. 2001; 164(3):447-454.
• [38]Castile R, Filbrun D, Flucke R, Franklin W, McCoy K. Adult-type pulmonary function tests in infants without respiratory disease. Pediatr Pulmonol. 2000; 30(3):215-227.
• [39]Gappa M, Colin AA, Goetz I, Stocks J. Passive respiratory mechanics: the occlusion techniques. Eur Respir J. 2001; 17(1):141-148.
• [40]Stocks J, Godfrey S, Beardsmore C, Bar-Yishay E, Castile R. Plethysmographic measurements of lung volume and airway resistance. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society. Eur Respir J. 2001; 17(2):302-312.
• [41]Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009; 42(2):377-381.
• [42]Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959; 22(4):719-748.
• [43]Davis SD, Rosenfeld M, Kerby GS, Brumback L, Kloster MH, Acton JD et al.. Multicenter evaluation of infant lung function tests as cystic fibrosis clinical trial endpoints. Am J Respir Crit Care Med. 2010; 182(11):1387-1397.
• [44]Kerby GS, Rosenfeld M, Ren CL, Mayer OH, Brumback L, Castile R et al.. Lung function distinguishes preschool children with CF from healthy controls in a multi-center setting. Pediatr Pulmonol. 2012; 47(6):597-605.
• [45]Bhattacharya S, Go D, Krenitsky DL, Huyck HL, Solleti SK, Lunger VA et al.. Genome-wide transcriptional profiling reveals connective tissue mast cell accumulation in bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2012; 186(4):349-358.
• [46]Ehrmann DC, Rose K, Calcutt MW, Beller AB, Hill S, Rogers TJ et al.. Glutathionylated gammaG and gammaA subunits of hemoglobin F: a novel post-translational modification found in extremely premature infants by LC-MS and nanoLC-MS/MS. J Mass Spectrom. 2014; 49(2):178-183.
• [47]Levy PT, Sanchez Mejia AA, Machefsky A, Fowler S, Holland MR, Singh GK. Normal ranges of right ventricular systolic and diastolic strain measures in children: a systematic review and meta-analysis. J Am Soc Echocardiogr. 2014; 27(5):549.
• [48]Groh GK, Levy PT, Holland MR, Murphy JJ, Sekarski TJ, Myers CL et al.. Doppler echocardiography inaccurately estimates right ventricular pressure in children with elevated right heart pressure. J Am Soc Echocardiogr. 2014; 27(2):163-171.
• [49]Levy PT, Holland MR, Sekarski TJ, Hamvas A, Singh GK. Feasibility and reproducibility of systolic right ventricular strain measurement by speckle-tracking echocardiography in premature infants. J Am Soc Echocardiogr. 2013; 26(10):1201-1213.
• [50]Singh GK, Levy PT, Holland MR, Hamvas A. Novel methods for assessment of right heart structure and function in pulmonary hypertension. Clin Perinatol. 2012; 39(3):685-701.
• [51]Ulm LN, Hamvas A, Ferkol TW, Rodriguez OM, Cleveland CM, Linneman LA et al.. Sources of methodological variability in phase angles from respiratory inductance plethysmography in preterm infants. Ann Am Thor Soc. 2014; 11(5):753-760.