Blood Cytokine Profiles Associated with Distinct Patterns of Bronchopulmonary Dysplasia among Extremely Low Birth Weight Infants

doi:10.1016/j.jpeds.2016.03.058

Blood Cytokine Profiles Associated with Distinct Patterns of Bronchopulmonary Dysplasia among Extremely Low Birth Weight Infants

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Abstract

Objective To explore differences in blood cytokine profiles among distinct bronchopulmonary dysplasia (BPD) patterns. Study design We evaluated blood spots collected from 943 infants born at ≤1000 g and surviving to 28 days on postnatal days 1, 3, 7, 14, and 21 for 25 cytokines. Infants were assigned to the following lung disease patterns: (1) no lung disease (NLD); (2) respiratory distress syndrome without BPD; (3) classic BPD (persistent exposure to supplemental oxygen until 28 days of age); or (4) atypical BPD (period without supplemental oxygen before 28 days). Median cytokine levels for infants with BPD were compared with the IQR of results among infants with NLD. Results The distribution of enrolled infants by group was as follows: 69 (NLD), 73 (respiratory distress syndrome), 381 (classic BPD), and 160 (atypical BPD). The remaining 260 infants could not be classified because of missing data (104) or not fitting a predefined pattern (156). Median levels of 3 cytokines (elevated interleukin [IL]-8, matrix metalloproteinase-9; decreased granulocyte macrophage colony-stimulating factor) fell outside the IQR for at least 2 time points in both infants with atypical and classic BPD. Profiles of 7 cytokines (IL-6, IL-10, IL-18, macrophage inflammatory protein-1α, C-reactive protein, brain-derived neurotrophic factor, regulated on activation, normal T cell expressed and secreted) differed between infants with classic and atypical BPD. Conclusions Blood cytokine profiles may differ between infants developing classic and atypical BPD. These dissimilarities suggest the possibility that differing mechanisms could explain the varied patterns of pathophysiology of lung disease in extremely premature infants.

Original language	English
Pages (from-to)	45-51.e5
Journal	Journal of Pediatrics
Volume	174
DOIs	https://doi.org/10.1016/j.jpeds.2016.03.058
State	Published - Jul 1 2016

Bibliographical note

Funding Information:
The Neonatal Research Network's Cytokines Study was supported by the National Institutes of Health (NIH; M01 RR30 , M01 RR32 , M01 RR39 , M01 RR70 , M01 RR80 , M01 RR633 , M01 RR750 , M01 RR997 , M01 RR6022 , M01 RR7122 , M01 RR8084 , M01 RR16587 ), the NICHD ( U01 HD36790 , U10 HD21364 , U10 HD21373 , U10 HD21385 , U10 HD21397 , U10 HD21415 , U10 HD27851 , U10 HD27853 , U10 HD27856 , U10 HD27871 , U10 HD27880 , U10 HD27881 , U10 HD27904 , U10 HD34216 , U10 HD40461 , U10 HD40492 , U10 HD40498 , U10 HD40689 ), and the Centers for Disease Control and Prevention (CDC; Interagency Agreement Y1-HD-5000-01). C.D. is supported by NICHD (1 U10 HD 068263). Participating sites collected data and transmitted it to RTI International, the data coordinating center for the network, which stored, managed, and analyzed the data for this study. Although NICHD and CDC staff did have input into the study design, conduct, analysis, and manuscript drafting, the content is solely the responsibility of the authors and does not necessarily represent the official views of NICHD or CDC. The authors declare no conflicts of interest.

Publisher Copyright:
© 2016 Elsevier Inc.

Keywords

chronic lung disease
inflammatory markers
premature infant
respiratory distress syndrome

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health

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10.1016/j.jpeds.2016.03.058

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@article{d35f1975fb3040e09d5e5adb9915d7fe,

title = "Blood Cytokine Profiles Associated with Distinct Patterns of Bronchopulmonary Dysplasia among Extremely Low Birth Weight Infants",

abstract = "Objective To explore differences in blood cytokine profiles among distinct bronchopulmonary dysplasia (BPD) patterns. Study design We evaluated blood spots collected from 943 infants born at ≤1000 g and surviving to 28 days on postnatal days 1, 3, 7, 14, and 21 for 25 cytokines. Infants were assigned to the following lung disease patterns: (1) no lung disease (NLD); (2) respiratory distress syndrome without BPD; (3) classic BPD (persistent exposure to supplemental oxygen until 28 days of age); or (4) atypical BPD (period without supplemental oxygen before 28 days). Median cytokine levels for infants with BPD were compared with the IQR of results among infants with NLD. Results The distribution of enrolled infants by group was as follows: 69 (NLD), 73 (respiratory distress syndrome), 381 (classic BPD), and 160 (atypical BPD). The remaining 260 infants could not be classified because of missing data (104) or not fitting a predefined pattern (156). Median levels of 3 cytokines (elevated interleukin [IL]-8, matrix metalloproteinase-9; decreased granulocyte macrophage colony-stimulating factor) fell outside the IQR for at least 2 time points in both infants with atypical and classic BPD. Profiles of 7 cytokines (IL-6, IL-10, IL-18, macrophage inflammatory protein-1α, C-reactive protein, brain-derived neurotrophic factor, regulated on activation, normal T cell expressed and secreted) differed between infants with classic and atypical BPD. Conclusions Blood cytokine profiles may differ between infants developing classic and atypical BPD. These dissimilarities suggest the possibility that differing mechanisms could explain the varied patterns of pathophysiology of lung disease in extremely premature infants.",

keywords = "chronic lung disease, inflammatory markers, premature infant, respiratory distress syndrome",

author = "D'Angio, {Carl T.} and Namasivayam Ambalavanan and Carlo, {Waldemar A.} and McDonald, {Scott A.} and Kristin Skogstrand and Hougaard, {David M.} and Seetha Shankaran and Goldberg, {Ronald N.} and Ehrenkranz, {Richard A.} and Tyson, {Jon E.} and Stoll, {Barbara J.} and Abhik Das and Higgins, {Rosemary D.} and Jobe, {Alan H.} and Laptook, {Abbot R.} and William Oh and Rubin, {Lewis P.} and Hensman, {Angelita M.} and Fanaroff, {Avroy A.} and Walsh, {Michele C.} and Newman, {Nancy S.} and Siner, {Bonnie S.} and Donovan, {Edward F.} and Vivek Narendran and Barbara Alexander and Cathy Grisby and Jody Hessling and Mersmann, {Marcia Worley} and Mincey, {Holly L.} and Cotten, {C. Michael} and Auten, {Kathy J.} and Hale, {Ellen C.} and Wright, {Linda L.} and Yaffe, {Sumner J.} and McClure, {Elizabeth M.} and Poindexter, {Brenda B.} and Lemons, {James A.} and Appel, {Diana D.} and Herron, {Dianne E.} and Wilson, {Leslie D.} and Poole, {W. Kenneth} and Hastings, {Betty K.} and Zaterka-Baxter, {Kristin M.} and {O'Donnell Auman}, Jeanette and Schaefer, {Scott E.} and Stevenson, {David K.} and {Van Meurs}, {Krisa P.} and Ball, {M. Bethany} and Collins, {Monica V.} and Bada, {Henrietta S.}",

note = "Funding Information: The Neonatal Research Network's Cytokines Study was supported by the National Institutes of Health (NIH; M01 RR30 , M01 RR32 , M01 RR39 , M01 RR70 , M01 RR80 , M01 RR633 , M01 RR750 , M01 RR997 , M01 RR6022 , M01 RR7122 , M01 RR8084 , M01 RR16587 ), the NICHD ( U01 HD36790 , U10 HD21364 , U10 HD21373 , U10 HD21385 , U10 HD21397 , U10 HD21415 , U10 HD27851 , U10 HD27853 , U10 HD27856 , U10 HD27871 , U10 HD27880 , U10 HD27881 , U10 HD27904 , U10 HD34216 , U10 HD40461 , U10 HD40492 , U10 HD40498 , U10 HD40689 ), and the Centers for Disease Control and Prevention (CDC; Interagency Agreement Y1-HD-5000-01). C.D. is supported by NICHD (1 U10 HD 068263). Participating sites collected data and transmitted it to RTI International, the data coordinating center for the network, which stored, managed, and analyzed the data for this study. Although NICHD and CDC staff did have input into the study design, conduct, analysis, and manuscript drafting, the content is solely the responsibility of the authors and does not necessarily represent the official views of NICHD or CDC. The authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = jul,

day = "1",

doi = "10.1016/j.jpeds.2016.03.058",

language = "English",

volume = "174",

pages = "45--51.e5",

}

TY - JOUR

T1 - Blood Cytokine Profiles Associated with Distinct Patterns of Bronchopulmonary Dysplasia among Extremely Low Birth Weight Infants

AU - D'Angio, Carl T.

AU - Ambalavanan, Namasivayam

AU - Carlo, Waldemar A.

AU - McDonald, Scott A.

AU - Skogstrand, Kristin

AU - Hougaard, David M.

AU - Shankaran, Seetha

AU - Goldberg, Ronald N.

AU - Ehrenkranz, Richard A.

AU - Tyson, Jon E.

AU - Stoll, Barbara J.

AU - Das, Abhik

AU - Higgins, Rosemary D.

AU - Jobe, Alan H.

AU - Laptook, Abbot R.

AU - Oh, William

AU - Rubin, Lewis P.

AU - Hensman, Angelita M.

AU - Fanaroff, Avroy A.

AU - Walsh, Michele C.

AU - Newman, Nancy S.

AU - Siner, Bonnie S.

AU - Donovan, Edward F.

AU - Narendran, Vivek

AU - Alexander, Barbara

AU - Grisby, Cathy

AU - Hessling, Jody

AU - Mersmann, Marcia Worley

AU - Mincey, Holly L.

AU - Cotten, C. Michael

AU - Auten, Kathy J.

AU - Hale, Ellen C.

AU - Wright, Linda L.

AU - Yaffe, Sumner J.

AU - McClure, Elizabeth M.

AU - Poindexter, Brenda B.

AU - Lemons, James A.

AU - Appel, Diana D.

AU - Herron, Dianne E.

AU - Wilson, Leslie D.

AU - Poole, W. Kenneth

AU - Hastings, Betty K.

AU - Zaterka-Baxter, Kristin M.

AU - O'Donnell Auman, Jeanette

AU - Schaefer, Scott E.

AU - Stevenson, David K.

AU - Van Meurs, Krisa P.

AU - Ball, M. Bethany

AU - Collins, Monica V.

AU - Bada, Henrietta S.

N1 - Funding Information: The Neonatal Research Network's Cytokines Study was supported by the National Institutes of Health (NIH; M01 RR30 , M01 RR32 , M01 RR39 , M01 RR70 , M01 RR80 , M01 RR633 , M01 RR750 , M01 RR997 , M01 RR6022 , M01 RR7122 , M01 RR8084 , M01 RR16587 ), the NICHD ( U01 HD36790 , U10 HD21364 , U10 HD21373 , U10 HD21385 , U10 HD21397 , U10 HD21415 , U10 HD27851 , U10 HD27853 , U10 HD27856 , U10 HD27871 , U10 HD27880 , U10 HD27881 , U10 HD27904 , U10 HD34216 , U10 HD40461 , U10 HD40492 , U10 HD40498 , U10 HD40689 ), and the Centers for Disease Control and Prevention (CDC; Interagency Agreement Y1-HD-5000-01). C.D. is supported by NICHD (1 U10 HD 068263). Participating sites collected data and transmitted it to RTI International, the data coordinating center for the network, which stored, managed, and analyzed the data for this study. Although NICHD and CDC staff did have input into the study design, conduct, analysis, and manuscript drafting, the content is solely the responsibility of the authors and does not necessarily represent the official views of NICHD or CDC. The authors declare no conflicts of interest. Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Objective To explore differences in blood cytokine profiles among distinct bronchopulmonary dysplasia (BPD) patterns. Study design We evaluated blood spots collected from 943 infants born at ≤1000 g and surviving to 28 days on postnatal days 1, 3, 7, 14, and 21 for 25 cytokines. Infants were assigned to the following lung disease patterns: (1) no lung disease (NLD); (2) respiratory distress syndrome without BPD; (3) classic BPD (persistent exposure to supplemental oxygen until 28 days of age); or (4) atypical BPD (period without supplemental oxygen before 28 days). Median cytokine levels for infants with BPD were compared with the IQR of results among infants with NLD. Results The distribution of enrolled infants by group was as follows: 69 (NLD), 73 (respiratory distress syndrome), 381 (classic BPD), and 160 (atypical BPD). The remaining 260 infants could not be classified because of missing data (104) or not fitting a predefined pattern (156). Median levels of 3 cytokines (elevated interleukin [IL]-8, matrix metalloproteinase-9; decreased granulocyte macrophage colony-stimulating factor) fell outside the IQR for at least 2 time points in both infants with atypical and classic BPD. Profiles of 7 cytokines (IL-6, IL-10, IL-18, macrophage inflammatory protein-1α, C-reactive protein, brain-derived neurotrophic factor, regulated on activation, normal T cell expressed and secreted) differed between infants with classic and atypical BPD. Conclusions Blood cytokine profiles may differ between infants developing classic and atypical BPD. These dissimilarities suggest the possibility that differing mechanisms could explain the varied patterns of pathophysiology of lung disease in extremely premature infants.

AB - Objective To explore differences in blood cytokine profiles among distinct bronchopulmonary dysplasia (BPD) patterns. Study design We evaluated blood spots collected from 943 infants born at ≤1000 g and surviving to 28 days on postnatal days 1, 3, 7, 14, and 21 for 25 cytokines. Infants were assigned to the following lung disease patterns: (1) no lung disease (NLD); (2) respiratory distress syndrome without BPD; (3) classic BPD (persistent exposure to supplemental oxygen until 28 days of age); or (4) atypical BPD (period without supplemental oxygen before 28 days). Median cytokine levels for infants with BPD were compared with the IQR of results among infants with NLD. Results The distribution of enrolled infants by group was as follows: 69 (NLD), 73 (respiratory distress syndrome), 381 (classic BPD), and 160 (atypical BPD). The remaining 260 infants could not be classified because of missing data (104) or not fitting a predefined pattern (156). Median levels of 3 cytokines (elevated interleukin [IL]-8, matrix metalloproteinase-9; decreased granulocyte macrophage colony-stimulating factor) fell outside the IQR for at least 2 time points in both infants with atypical and classic BPD. Profiles of 7 cytokines (IL-6, IL-10, IL-18, macrophage inflammatory protein-1α, C-reactive protein, brain-derived neurotrophic factor, regulated on activation, normal T cell expressed and secreted) differed between infants with classic and atypical BPD. Conclusions Blood cytokine profiles may differ between infants developing classic and atypical BPD. These dissimilarities suggest the possibility that differing mechanisms could explain the varied patterns of pathophysiology of lung disease in extremely premature infants.

KW - chronic lung disease

KW - inflammatory markers

KW - premature infant

KW - respiratory distress syndrome

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UR - http://www.scopus.com/inward/citedby.url?scp=84964241120&partnerID=8YFLogxK

U2 - 10.1016/j.jpeds.2016.03.058

DO - 10.1016/j.jpeds.2016.03.058

M3 - Article

C2 - 27117196

AN - SCOPUS:84964241120

VL - 174

SP - 45-51.e5

ER -

Blood Cytokine Profiles Associated with Distinct Patterns of Bronchopulmonary Dysplasia among Extremely Low Birth Weight Infants

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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