Urine Desmosine as a Novel Biomarker for Bronchopulmonary Dysplasia and Postprematurity Respiratory Disease in Extremely Preterm or Low Birth Weight Infants

Abstract Objective  This study aimed to evaluate whether elevated urine desmosine levels at 3 weeks of age were associated with severe radiological findings, bronchopulmonary dysplasia (BPD), and post-prematurity respiratory disease (PRD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants. Study Design  This study recruited 37 EP (22–27 completed weeks) or ELBW (<1,000 g) infants. Urine was collected between 21 and 28 postnatal days, and desmosine was measured using an enzyme-linked immunosorbent assay kit; the urine creatinine level was also measured. Bubbly/cystic lungs were characterized by emphysematous chest X-rays on postnatal day 28. Furthermore, provision of supplemental oxygen or positive-pressure respiratory support at 40 weeks' postmenstrual age defined BPD, and increased medical utilization at 18 months of corrected age defined PRD. The desmosine/creatinine threshold was determined by receiver operating characteristic analysis. The adjusted risk and 95% confidence interval (CI) for elevated urine desmosine/creatinine levels were estimated by logistic regression analysis. Results  Elevated urine desmosine/creatinine levels higher than the threshold were significantly associated with bubbly/cystic lungs (8/13 [61.5%] vs. 2/24 [8.3%], p  = 0.001), BPD (10/13 [76.9%] vs. 8/24 [33.3%], p  = 0.02), and PRD (6/13 [46.2%] vs. 2/24 [8.3%], p  = 0.01). After adjusting for gestational age, birth weight, and sex, the urine desmosine/creatinine levels were significantly higher in those who were highly at risk of bubbly/cystic lungs (odds ratio [OR], 13.2; 95% CI, 1.67–105) and PRD (OR, 13.8; 95% CI, 1.31–144). Conclusion  Elevated urine desmosine/creatinine levels on the third postnatal week were associated with bubbly/cystic lungs on day 28 and PRD at 18 months of corrected age in EP or ELBW infants. Key Points Urine desmosine was prospectively measured in 3-week-old EP/ELBW infants. Elevated urine desmosine levels were associated with emphysematous radiological findings on day 28, PRD at 18 months of corrected age. Urine desmosine may be a promising biomarker indicating lung damage in EP/ELBW infants.

[1]  J. Shiraishi,et al.  Intrauterine Ureaplasma is associated with small airway obstruction in extremely preterm infants , 2022, Pediatric pulmonology.

[2]  E. Jensen,et al.  Online clinical tool to estimate risk of bronchopulmonary dysplasia in extremely preterm infants , 2022, Archives of Disease in Childhood.

[3]  K. Hirata,et al.  The status of chronic lung disease diagnosis in Japan: Secondary publication. , 2022, Pediatrics international : official journal of the Japan Pediatric Society.

[4]  S. Verhulst,et al.  Lung imaging in bronchopulmonary dysplasia: a systematic review. , 2020, Respiratory medicine.

[5]  M. O’Reilly,et al.  Early Neonatal Oxygen Exposure Predicts Pulmonary Morbidity and Functional Deficits at 1 Year. , 2020, The Journal of pediatrics.

[6]  E. Baraldi,et al.  Present and Future of Bronchopulmonary Dysplasia , 2020, Journal of clinical medicine.

[7]  Tsutomu Takahashi,et al.  Bubbly and cystic appearance on chest radiograph of extremely preterm infants with bronchopulmonary dysplasia is associated with wheezing disorder , 2020, Acta paediatrica.

[8]  B. Poindexter,et al.  The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach , 2019, American journal of respiratory and critical care medicine.

[9]  Sean B Fain,et al.  Neonatal Pulmonary Magnetic Resonance Imaging of Bronchopulmonary Dysplasia Predicts Short‐Term Clinical Outcomes , 2018, American journal of respiratory and critical care medicine.

[10]  L. Doyle,et al.  An update on pulmonary and neurodevelopmental outcomes of bronchopulmonary dysplasia. , 2018, Seminars in perinatology.

[11]  T. Raju,et al.  Bronchopulmonary Dysplasia: Executive Summary of a Workshop , 2018, The Journal of pediatrics.

[12]  Jae Seung Lee,et al.  Urinary desmosine is associated with emphysema severity and frequent exacerbation in patients with COPD , 2018, Respirology.

[13]  P. Shaw,et al.  Bronchopulmonary Dysplasia and Perinatal Characteristics Predict 1-Year Respiratory Outcomes in Newborns Born at Extremely Low Gestational Age: A Prospective Cohort Study. , 2017, The Journal of pediatrics.

[14]  L. Doyle,et al.  Ventilation in Extremely Preterm Infants and Respiratory Function at 8 Years , 2017, The New England journal of medicine.

[15]  M. Nishihara,et al.  Longitudinal impairment of lung function in school‐age children with extremely low birth weights , 2017, Pediatric pulmonology.

[16]  Shoo K. Lee,et al.  Revisiting the Definition of Bronchopulmonary Dysplasia: Effect of Changing Panoply of Respiratory Support for Preterm Neonates , 2017, JAMA pediatrics.

[17]  T. Baba,et al.  Evaluation of urinary desmosines as a noninvasive diagnostic biomarker in patients with idiopathic pleuroparenchymal fibroelastosis (PPFE). , 2017, Respiratory medicine.

[18]  D. Black,et al.  Early Cumulative Supplemental Oxygen Predicts Bronchopulmonary Dysplasia in High Risk Extremely Low Gestational Age Newborns. , 2016, The Journal of pediatrics.

[19]  H. Tiddens,et al.  Lung CT imaging in patients with bronchopulmonary dysplasia: A systematic review , 2016, Pediatric pulmonology.

[20]  M. Tamura,et al.  Bubbly and cystic appearance in chronic lung disease: Is this diagnosed as Wilson–Mikity syndrome? , 2016, Pediatrics international : official journal of the Japan Pediatric Society.

[21]  M. Nishihara,et al.  Perinatal factors associated with long-term respiratory sequelae in extremely low birthweight infants , 2015, Archives of Disease in Childhood: Fetal and Neonatal Edition.

[22]  Y. Kanda,et al.  Investigation of the freely available easy-to-use software ‘EZR' for medical statistics , 2012, Bone Marrow Transplantation.

[23]  F. Accurso,et al.  Urinary desmosine: A biomarker of structural lung injury during CF pulmonary exacerbation , 2012, Pediatric pulmonology.

[24]  N. Thomson,et al.  Clinical validity of plasma and urinary desmosine as biomarkers for chronic obstructive pulmonary disease , 2012, Thorax.

[25]  R. Ehrenkranz,et al.  Patterns of Respiratory Disease During the First 2 Postnatal Weeks in Extremely Premature Infants , 2009, Pediatrics.

[26]  G. Turino,et al.  Desmosine as a biomarker of elastin degradation in COPD: current status and future directions , 2008, European Respiratory Journal.

[27]  M. Walsh,et al.  Safety, Reliability, and Validity of a Physiologic Definition of Bronchopulmonary Dysplasia , 2003, Journal of Perinatology.

[28]  Stark Ar 超出生体重児に対する早期デキサメサゾン投与の有用性 : National Institute of Child Health and Human Development Neonatal research Network報告 (海外誌掲載論文の和文概要とそれに対するコメント) , 2001 .

[29]  D. Phelps,et al.  Atypical Chronic Lung Disease Patterns in Neonates , 1999, Pediatrics.

[30]  M. Nakayama,et al.  Increased leukocyte elastase of the tracheal aspirate at birth and neonatal pulmonary emphysema. , 1993, Pediatrics.

[31]  J. Tomashefski,et al.  Risk factors for the degradation of lung elastic fibers in the ventilated neonate. Implications for impaired lung development in bronchopulmonary dysplasia. , 1992, The American review of respiratory disease.

[32]  A. Fanaroff,et al.  Altered urinary excretion of elastin cross-links in premature infants who develop bronchopulmonary dysplasia. , 1985, The American review of respiratory disease.

[33]  L. Monte,et al.  [Bronchopulmonary dysplasia]. , 2005, Jornal de pediatria.