Correlation of Polymorphonuclear Cell Burden and Microbial Growth to the Inflammatory Cytokines in Tracheal Aspirates from Ventilated Preterm Infants

Sophia Baig; Pragnya Das; Niharika Podaralla; Alan Evangelista; Ishminder Kaur; Vineet Bhandari

doi:10.1055/a-2033-5536

American Journal of Perinatology, Table of Contents

Am J Perinatol 2024; 41(10): 1388-1395
DOI: 10.1055/a-2033-5536

Original Article

Correlation of Polymorphonuclear Cell Burden and Microbial Growth to the Inflammatory Cytokines in Tracheal Aspirates from Ventilated Preterm Infants

Sophia Baig

¹Section of Neonatal-Perinatal Medicine, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania

,

Pragnya Das

¹Section of Neonatal-Perinatal Medicine, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania

,

Niharika Podaralla

¹Section of Neonatal-Perinatal Medicine, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania

,

Alan Evangelista

²Department of Pathology & Laboratory Medicine, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania

,

Ishminder Kaur

³Section of Infectious Diseases, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania

,

Vineet Bhandari

¹Section of Neonatal-Perinatal Medicine, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania

› Author Affiliations

Abstract

Objective The significance of the presence of microorganisms and polymorphonuclear cells in the tracheal aspirates (TAs) of ventilated preterm infants is not well known. Our aim was to correlate information about the presence of polymorphonuclear cells with microbial growth and the cytokine milieu in the TAs of infants who have been intubated for >7 days.

Study Design TAs were collected from infants who had been intubated for 7 days or longer. Respiratory cultures were performed, and infants were stratified based on the presence and abundance of polymorphonuclear cells and microbial growth. Cytokines were measured in the TAs of each of the respective groups.

Results In the 19 infants whose TAs were collected, the presence of at least moderate WBC with presence of microbial growth was positively associated with the presence of interleukin (IL)-10, IL-1β, IL-8, and tumor necrosis factor (TNF)-α. The presence of at least moderate WBC, with or without microbial growth, was correlated positively with the presence of IL-8 and TNF-α.

Conclusion There are higher levels of proinflammatory cytokines (especially, IL-10, IL-1β, and TNF-α) in TAs with higher cell counts and presence of microbial growth. The findings suggest that the presence of microbial growth correlated with inflammatory burden and warrant a larger study to see if treatment of microbial growth can ameliorate the inflammatory burden.

Key Points

Concomitant evaluation of inflammatory cells, microbial growth, and cytokines in tracheal aspirates.
Moderate TA WBC with presence of microbial growth associated with IL-10, IL-1β, IL-8, and TNF-α.
Moderate TA WBC, with/without microbial growth, correlated with the presence of IL-8 and TNF-α.
Higher levels of IL-10, IL-1β, and TNF-α correlated with higher TA cell counts and microbial growth.

Keywords

cytokines - cell counts - tracheal aspirate cultures - preterm newborn

Full Text

References

References
1 Lui K, Lee SK, Kusuda S. et al; International Network for Evaluation of Outcomes (iNeo) of neonates Investigators. Trends in outcomes for neonates born very preterm and very low birth weight in 11 high-income countries. J Pediatr 2019; 215: 32-40.e14
2 Gregory KE, Deforge CE, Natale KM, Phillips M, Van Marter LJ. Necrotizing enterocolitis in the premature infant: neonatal nursing assessment, disease pathogenesis, and clinical presentation. Adv Neonatal Care 2011; 11 (03) 155-164 , quiz 165–166
3 Stoll BJ, Hansen NI, Bell EF. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA 2015; 314 (10) 1039-1051
4 Greenough A, Rossor TE, Sundaresan A, Murthy V, Milner AD. Synchronized mechanical ventilation for respiratory support in newborn infants. Cochrane Database Syst Rev 2016; 9 (09) CD000456
5 Kirpalani H, Ratcliffe SJ, Keszler M. et al; SAIL Site Investigators. Effect of sustained inflations vs intermittent positive pressure ventilation on bronchopulmonary dysplasia or death among extremely preterm infants: the SAIL randomized clinical trial. JAMA 2019; 321 (12) 1165-1175
6 Craven DE, Hjalmarson KI. Ventilator-associated tracheobronchitis and pneumonia: thinking outside the box. Clin Infect Dis 2010; 51 (suppl): S59-S66
7 Craven DE, Hudcova J, Craven KA, Scopa C, Lei Y. Antibiotic treatment of ventilator-associated tracheobronchitis: to treat or not to treat?. Curr Opin Crit Care 2014; 20 (05) 532-541
8 Koulenti D, Arvaniti K, Judd M. et al. Ventilator-associated tracheobronchitis: to treat or not to treat?. Antibiotics (Basel) 2020; 9 (02) 51
9 Tamma PD, Turnbull AE, Milstone AM, Lehmann CU, Sydnor ER, Cosgrove SE. Ventilator-associated tracheitis in children: does antibiotic duration matter?. Clin Infect Dis 2011; 52 (11) 1324-1331
10 Baltimore RS. The difficulty of diagnosing ventilator-associated pneumonia. Pediatrics 2003; 112 (6 Pt 1): 1420-1421
11 Slagle TA, Bifano EM, Wolf JW, Gross SJ. Routine endotracheal cultures for the prediction of sepsis in ventilated babies. Arch Dis Child 1989; 64 (1 Spec No): 34-38
12 Aghai ZH, Kode A, Saslow JG. et al. Azithromycin suppresses activation of nuclear factor-kappa B and synthesis of pro-inflammatory cytokines in tracheal aspirate cells from premature infants. Pediatr Res 2007; 62 (04) 483-488
13 Ambalavanan N, Carlo WA, D'Angio CT. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Cytokines associated with bronchopulmonary dysplasia or death in extremely low birth weight infants. Pediatrics 2009; 123 (04) 1132-1141
14 Balany J, Bhandari V. Understanding the impact of infection, inflammation, and their persistence in the pathogenesis of bronchopulmonary dysplasia. Front Med (Lausanne) 2015; 2: 90
15 Bhandari A, Bhandari V. Biomarkers in bronchopulmonary dysplasia. Paediatr Respir Rev 2013; 14 (03) 173-179
16 D'Angio CT, Basavegowda K, Avissar NE, Finkelstein JN, Sinkin RA. Comparison of tracheal aspirate and bronchoalveolar lavage specimens from premature infants. Biol Neonate 2002; 82 (03) 145-149
17 De Dooy J, Ieven M, Stevens W, De Clerck L, Mahieu L. High levels of CXCL8 in tracheal aspirate samples taken at birth are associated with adverse respiratory outcome only in preterm infants younger than 28 weeks gestation. Pediatr Pulmonol 2007; 42 (03) 193-203
18 Jónsson B, Tullus K, Brauner A, Lu Y, Noack G. Early increase of TNF alpha and IL-6 in tracheobronchial aspirate fluid indicator of subsequent chronic lung disease in preterm infants. Arch Dis Child Fetal Neonatal Ed 1997; 77 (03) F198-F201
19 Laughon MM, Langer JC, Bose CL. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Prediction of bronchopulmonary dysplasia by postnatal age in extremely premature infants. Am J Respir Crit Care Med 2011; 183 (12) 1715-1722
20 Liao J, Kapadia VS, Brown LS. et al. The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia. Nat Commun 2015; 6: 8977
21 Jensen EA, Dysart K, Gantz MG. et al. The diagnosis of bronchopulmonary dysplasia in very preterm infants. an evidence-based approach. Am J Respir Crit Care Med 2019; 200 (06) 751-759
22 Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163 (07) 1723-1729
23 The Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Arch Ophthalmol 1984; 102 (08) 1130-1134
24 Sheth S, Goto L, Bhandari V, Abraham B, Mowes A. Factors associated with development of early and late pulmonary hypertension in preterm infants with bronchopulmonary dysplasia. J Perinatol 2020; 40 (01) 138-148
25 Mitra S, Scrivens A, von Kursell AM, Disher T. Early treatment versus expectant management of hemodynamically significant patent ductus arteriosus for preterm infants. Cochrane Database Syst Rev 2020; 12 (12) CD013278
26 Ingolfsland EC, Gonzalez-Villamizar JD, Moore J. et al. Improving management of ventilator associated tracheitis in a level IV NICU. J Perinatol 2022; 42 (09) 1260-1265 [ Erratum in: J Perinatol 2022; PMID: 35449445]
27 Munshi UK, Niu JO, Siddiq MM, Parton LA. Elevation of interleukin-8 and interleukin-6 precedes the influx of neutrophils in tracheal aspirates from preterm infants who develop bronchopulmonary dysplasia. Pediatr Pulmonol 1997; 24 (05) 331-336
28 Thompson A, Bhandari V. Pulmonary biomarkers of bronchopulmonary dysplasia. Biomark Insights 2008; 3: 361-373
29 von Bismarck P, Claass A, Schickor C, Krause MF, Rose-John S. Altered pulmonary interleukin-6 signaling in preterm infants developing bronchopulmonary dysplasia. Exp Lung Res 2008; 34 (10) 694-706
30 Rojas JM, Avia M, Martín V, Sevilla N. IL-10: a multifunctional cytokine in viral infections. J Immunol Res 2017; 2017: 6104054
31 Sheeran P, Jafri H, Carubelli C. et al. Elevated cytokine concentrations in the nasopharyngeal and tracheal secretions of children with respiratory syncytial virus disease. Pediatr Infect Dis J 1999; 18 (02) 115-122
32 Booth GR, Al-Hosni M, Ali A, Keenan WJ. The utility of tracheal aspirate cultures in the immediate neonatal period. J Perinatol 2009; 29 (07) 493-496

Supplementary Material

Supplementary Material