European Journal of Pediatrics

, Volume 176, Issue 5, pp 629–638 | Cite as

Clinical features and inflammatory markers in pediatric pneumonia: a prospective study

  • Are Stuwitz Berg
  • Christopher Stephen Inchley
  • Hans Olav Fjaerli
  • Truls Michael Leegaard
  • Morten Lindbaek
  • Britt Nakstad
Original Article

Abstract

In this prospective, observational study on previously healthy children <18 years, we aimed to study the diagnostic ability of clinical features and inflammatory markers to (i) predict pathologic chest radiography in suspected pneumonia and (ii) differentiate etiology in radiological proven pneumonia. In 394 cases of suspected pneumonia, 265 (67%) had radiographs consistent with pneumonia; 34/265 had proof of bacterial etiology. Of the cases, 86.5% had received pneumococcal conjugate vaccine. In suspected pneumonia, positive chest radiography was significantly associated with increasing C-reactive protein (CRP) values, higher age, and SpO2 ≤92% in multivariate logistic regression, OR 1.06 (95% CI 1.03 to 1.09), OR 1.09 (95% CI 1.00 to1.18), and OR 2.71 (95% CI 1.42 to 5.18), respectively. In proven pneumonia, bacterial pneumonia was significantly differentiated from viral/atypical pneumonia by increasing CRP values and SpO2 >92% in multivariate logistic regression, OR 1.09 (95% CI 1.05 to 1.14) and OR 0.23 (95% CI 0.06 to 0.82), respectively. Combining high CRP values (>80 mg/L) and elevated white blood cell (WBC) count provided specificity >85%, positive likelihood ratios >3, but sensitivity <46% for both radiographic proven and bacterial pneumonia.

Conclusion: With relatively high specificity and likelihood ratio CRP, WBC count and hypoxemia may be beneficial in ruling in a positive chest radiograph in suspected pneumonia and bacterial etiology in proven pneumonia, but with low sensitivity, the clinical utility is limited.

What is Known:

Pneumonia is recommended to be a clinical diagnosis, and neither clinical features nor inflammatory markers can reliably distinguish etiology.

The etiology of pneumonia has changed after routine pneumococcal conjugate vaccine.

What is New:

High CRP and WBC counts were associated with infiltrates in children with suspected pneumonia and with bacterial infection in proven pneumonia.

In the post-pneumococcal vaccination era, viral etiology is expected, and in cases of pneumonia with low CRP and WBC counts, a watch-and-wait strategy for antibiotic treatment may be applied.

Keywords

Pneumonia Clinical features Inflammatory markers Pneumococcal vaccination 

Abbreviations

ALRI

Acute lower respiratory tract infection

AUC

Area under the curve

CAP

Community-acquired pneumonia

CRP

C-reactive protein

IQR

Interquartile range

PCR

Polymerase chain reaction

ROCs

Receiver operating characteristics

WBC

White blood cells

Notes

Acknowledgements

We are grateful to all participating children and their parents and nurses and doctors on call for recruiting patients and collecting data. We thank Drs. R Bull and R Grotli at the Department for Radiology, Akershus University Hospital, for performing the radiological examinations; Dr. I Aaberge and A Aase for the pneumococcal serological analyses at the Department of Bacteriology and Immunology, the Norwegian Institute for Public Health; and Dr. Line Sletner at our department for the advise on statistical analyses and staff at the laboratories at Akershus University Hospital for performing the laboratory analyses.

Authors’ contributions

All authors provided substantial contributions to the study’s conception and design and acquisition, analysis, or interpretation of the data.

Drs. Berg, Inchley, Fjaerli, and Nakstad executed the clinical part of the work.

Dr. Leegaard was responsible for the microbiological laboratory analyses.

Dr. Lindbaek was responsible for the primary care part of the study.

Dr. Berg drafted the initial manuscript, and all other authors revised it critically for important intellectual content. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and approved by both the Regional Ethics Committee and the local Data Protection Officer. Furthermore, the study was in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Source of funding

The study was supported by research grants from Akershus University Hospital and South-Eastern Norway Regional Health Authority and grants from the Grimsgaard Foundation and the Norwegian Organization for Surveillance of Antimicrobial Resistance.

References

  1. 1.
    Angoulvant F, Levy C, Grimprel E, Varon E, Lorrot M, Biscardi S, Minodier P, Dommergues MA, Hees L, Gillet Y, Craiu I, Zenkhri F, Dubos F, Guen CG, Launay E, Martinot A, Cohen R (2014) Early impact of 13-valent pneumococcal conjugate vaccine on community-acquired pneumonia in children. Clin Infect Dis 58(7):918–924. doi: 10.1093/cid/ciu006 CrossRefPubMedGoogle Scholar
  2. 2.
    Berg AS, Inchley CS, Aase A, Fjaerli HO, Bull R, Aaberge I, Leegaard TM, Nakstad B (2016a) Etiology of pneumonia in a pediatric population with high pneumococcal vaccine coverage: a prospective study. Pediatr Infect Dis J 35(3):e69–e75. doi: 10.1097/INF.0000000000001009 CrossRefPubMedGoogle Scholar
  3. 3.
    Berg AS, Inchley CS, Fjaerli HO, Leegaard TM, Nakstad B (2016b) Microbial aetiology of paediatric pneumonia complicated with parapneumonic effusion in the era of pneumococcal vaccination. Infect Dis (Lond) 48(9):712–714. doi: 10.1080/23744235.2016.1192721 CrossRefGoogle Scholar
  4. 4.
    Bradley JS, Byington CL, Shah SS, Alverson B, Carter ER, Harrison C, Kaplan SL, Mace SE, McCracken GH Jr, Moore MR, St Peter SD, Stockwell JA, Swanson JT, Pediatric Infectious Diseases S, the Infectious Diseases Society of A (2011) The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis 53(7):e25–e76. doi: 10.1093/cid/cir531 CrossRefPubMedGoogle Scholar
  5. 5.
    Cherian T, Mulholland EK, Carlin JB, Ostensen H, Amin R, de Campo M, Greenberg D, Lagos R, Lucero M, Madhi SA, O’Brien KL, Obaro S, Steinhoff MC (2005) Standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies. Bull World Health Organ 83(5):353–359PubMedPubMedCentralGoogle Scholar
  6. 6.
    Chiappini E, Venturini E, Galli L, Novelli V, de Martino M (2013) Diagnostic features of community-acquired pneumonia in children: what’s new? Acta Paediatr Suppl 102(465):17–24. doi: 10.1111/apa.12502 CrossRefGoogle Scholar
  7. 7.
    Craig JC, Williams GJ, Jones M, Codarini M, Macaskill P, Hayen A, Irwig L, Fitzgerald DA, Isaacs D, McCaskill M (2010) The accuracy of clinical symptoms and signs for the diagnosis of serious bacterial infection in young febrile children: prospective cohort study of 15 781 febrile illnesses. BMJ 340:c1594. doi: 10.1136/bmj.c1594 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Don M, Canciani M, Korppi M (2010) Community-acquired pneumonia in children: what’s old? What’s new? Acta Paediatr 99(11):1602–1608. doi: 10.1111/j.1651-2227.2010.01924.x CrossRefPubMedGoogle Scholar
  9. 9.
    Elemraid MA, Rushton SP, Thomas MF, Spencer DA, Gennery AR, Clark JE (2014) Utility of inflammatory markers in predicting the aetiology of pneumonia in children. Diagn Microbiol Infect Dis 79(4):458–462. doi: 10.1016/j.diagmicrobio.2014.04.006 CrossRefPubMedGoogle Scholar
  10. 10.
    Esposito S, Bosis S, Cavagna R, Faelli N, Begliatti E, Marchisio P, Blasi F, Bianchi C, Principi N (2002) Characteristics of Streptococcus pneumoniae and atypical bacterial infections in children 2–5 years of age with community-acquired pneumonia. Clin Infect Dis 35(11):1345–1352. doi: 10.1086/344191 CrossRefPubMedGoogle Scholar
  11. 11.
    Flood RG, Badik J, Aronoff SC (2008) The utility of serum C-reactive protein in differentiating bacterial from nonbacterial pneumonia in children: a meta-analysis of 1230 children. Pediatr Infect Dis J 27(2):95–99. doi: 10.1097/INF.0b013e318157aced PubMedGoogle Scholar
  12. 12.
    Galetto-Lacour A, Alcoba G, Posfay-Barbe KM, Cevey-Macherel M, Gehri M, Ochs MM, Brookes RH, Siegrist CA, Gervaix A (2013) Elevated inflammatory markers combined with positive pneumococcal urinary antigen are a good predictor of pneumococcal community-acquired pneumonia in children. Pediatr Infect Dis J 32(11):1175–1179. doi: 10.1097/INF.0b013e31829ba62a CrossRefPubMedGoogle Scholar
  13. 13.
    Gove S (1997) Integrated management of childhood illness by outpatient health workers: technical basis and overview. The WHO Working Group on Guidelines for Integrated Management of the Sick Child. Bull World Health Organ 75(Suppl 1):7–24PubMedPubMedCentralGoogle Scholar
  14. 14.
    Harnden A, Perera R, Brueggemann AB, Mayon-White R, Crook DW, Thomson A, Mant D (2007) Respiratory infections for which general practitioners consider prescribing an antibiotic: a prospective study. Arch Dis Child 92(7):594–597. doi: 10.1136/adc.2007.116665 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Harris M, Clark J, Coote N, Fletcher P, Harnden A, McKean M, Thomson A (2011) British Thoracic Society guidelines for the management of community acquired pneumonia in children: update. Thorax 66(Suppl 2):ii1–i23. doi: 10.1136/thoraxjnl-2011-200598 CrossRefPubMedGoogle Scholar
  16. 16.
    Hazir T, Nisar YB, Qazi SA, Khan SF, Raza M, Zameer S, Masood SA (2006) Chest radiography in children aged 2–59 months diagnosed with non-severe pneumonia as defined by World Health Organization: descriptive multicentre study in Pakistan. BMJ 333(7569):629. doi: 10.1136/bmj.38915.673322.80 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Heiskanen-Kosma T, Korppi M (2000) Serum C-reactive protein cannot differentiate bacterial and viral aetiology of community-acquired pneumonia in children in primary healthcare settings. Scand J Infect Dis 32(4):399–402CrossRefPubMedGoogle Scholar
  18. 18.
    Hinchliffe R (1992) Reference values. In: Lilleyman J, Hann I (eds) Pediatric hematology, 2nd edn. Churchill Livingstone, Edinburgh, pp 1–22Google Scholar
  19. 19.
    Jain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C, Stockmann C, Anderson EJ, Grijalva CG, Self WH, Zhu Y, Patel A, Hymas W, Chappell JD, Kaufman RA, Kan JH, Dansie D, Lenny N, Hillyard DR, Haynes LM, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, Wunderink RG, Edwards KM, Pavia AT, McCullers JA, Finelli L, Team CES (2015) Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med 372(9):835–845. doi: 10.1056/NEJMoa1405870 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Juven T, Mertsola J, Toikka P, Virkki R, Leinonen M, Ruuskanen O (2001) Clinical profile of serologically diagnosed pneumococcal pneumonia. Pediatr Infect Dis J 20(11):1028–1033CrossRefPubMedGoogle Scholar
  21. 21.
    Korppi M, Heiskanen-Kosma T, Leinonen M (1997) White blood cells, C-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children. Eur Respir J 10(5):1125–1129CrossRefPubMedGoogle Scholar
  22. 22.
    Korppi M, Don M, Valent F, Canciani M (2008) The value of clinical features in differentiating between viral, pneumococcal and atypical bacterial pneumonia in children. Acta Paediatr 97(7):943–947. doi: 10.1111/j.1651-2227.2008.00789.x CrossRefPubMedGoogle Scholar
  23. 23.
    Koster MJ, Broekhuizen BD, Minnaard MC, Balemans WA, Hopstaken RM, de Jong PA, Verheij TJ (2013) Diagnostic properties of C-reactive protein for detecting pneumonia in children. Respir Med 107(7):1087–1093. doi: 10.1016/j.rmed.2013.04.012 CrossRefPubMedGoogle Scholar
  24. 24.
    Lowell DI, Lister G, Von Koss H, McCarthy P (1987) Wheezing in infants: the response to epinephrine. Pediatrics 79(6):939–945PubMedGoogle Scholar
  25. 25.
    Lynch T, Platt R, Gouin S, Larson C, Patenaude Y (2004) Can we predict which children with clinically suspected pneumonia will have the presence of focal infiltrates on chest radiographs? Pediatrics 113(3 Pt 1):e186–e189CrossRefPubMedGoogle Scholar
  26. 26.
    Mahabee-Gittens EM, Grupp-Phelan J, Brody AS, Donnelly LF, Bracey SE, Duma EM, Mallory ML, Slap GB (2005) Identifying children with pneumonia in the emergency department. Clin Pediatr (Phila) 44(5):427–435CrossRefGoogle Scholar
  27. 27.
    McIntosh K (2002) Community-acquired pneumonia in children. N Engl J Med 346(6):429–437. doi: 10.1056/NEJMra011994 CrossRefPubMedGoogle Scholar
  28. 28.
    van der Meer V, Neven AK, van den Broek PJ, Assendelft WJ (2005) Diagnostic value of C reactive protein in infections of the lower respiratory tract: systematic review. BMJ 331(7507):26. doi: 10.1136/bmj.38483.478183.EB CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Michelow IC, Olsen K, Lozano J, Rollins NK, Duffy LB, Ziegler T, Kauppila J, Leinonen M, McCracken GH Jr (2004) Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children. Pediatrics 113(4):701–707CrossRefPubMedGoogle Scholar
  30. 30.
    Neuman MI, Monuteaux MC, Scully KJ, Bachur RG (2011) Prediction of pneumonia in a pediatric emergency department. Pediatrics 128(2):246–253. doi: 10.1542/peds.2010-3367 CrossRefPubMedGoogle Scholar
  31. 31.
    Oostenbrink R, Thompson M, Lakhanpaul M, Steyerberg EW, Coad N, Moll HA (2013) Children with fever and cough at emergency care: diagnostic accuracy of a clinical model to identify children at low risk of pneumonia. Eur J Emerg Med 20(4):273–280. doi: 10.1097/MEJ.0b013e32835771fd CrossRefPubMedGoogle Scholar
  32. 32.
    Prat C, Dominguez J, Rodrigo C, Gimenez M, Azuara M, Jimenez O, Gali N, Ausina V (2003) Procalcitonin, C-reactive protein and leukocyte count in children with lower respiratory tract infection. Pediatr Infect Dis J 22(11):963–968. doi: 10.1097/01.inf.0000095197.72976.4f CrossRefPubMedGoogle Scholar
  33. 33.
    Rambaud-Althaus C, Althaus F, Genton B, D’Acremont V (2015) Clinical features for diagnosis of pneumonia in children younger than 5 years: a systematic review and meta-analysis. Lancet Infect Dis 15(4):439–450. doi: 10.1016/s1473-3099(15)70017-4 CrossRefPubMedGoogle Scholar
  34. 34.
    Rothrock SG, Green SM, Fanelli JM, Cruzen E, Costanzo KA, Pagane J (2001) Do published guidelines predict pneumonia in children presenting to an urban ED? Pediatr Emerg Care 17(4):240–243CrossRefPubMedGoogle Scholar
  35. 35.
    Shah S, Bachur R, Kim D, Neuman MI (2010) Lack of predictive value of tachypnea in the diagnosis of pneumonia in children. Pediatr Infect Dis J 29(5):406–409. doi: 10.1097/INF.0b013e3181cb45a7 CrossRefPubMedGoogle Scholar
  36. 36.
    Solevag AL, Eggen EH, Schroder J, Nakstad B (2013) Use of a modified pediatric early warning score in a department of pediatric and adolescent medicine. PLoS One 8(8):e72534. doi: 10.1371/journal.pone.0072534 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Toikka P, Irjala K, Juven T, Virkki R, Mertsola J, Leinonen M, Ruuskanen O (2000) Serum procalcitonin, C-reactive protein and interleukin-6 for distinguishing bacterial and viral pneumonia in children. Pediatr Infect Dis J 19(7):598–602CrossRefPubMedGoogle Scholar
  38. 38.
    Trogstad L, Ung G, Hagerup-Jenssen M, Cappelen I, Haugen IL, Feiring B (2012) The Norwegian immunisation register—SYSVAK. Euro Surveill 17 (16)Google Scholar
  39. 39.
    Van den Bruel A, Thompson MJ, Haj-Hassan T, Stevens R, Moll H, Lakhanpaul M, Mant D (2011) Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review. BMJ 342:d3082. doi: 10.1136/bmj.d3082 CrossRefPubMedGoogle Scholar
  40. 40.
    Virkki R, Juven T, Rikalainen H, Svedstrom E, Mertsola J, Ruuskanen O (2002) Differentiation of bacterial and viral pneumonia in children. Thorax 57(5):438–441CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Wingerter SL, Bachur RG, Monuteaux MC, Neuman MI (2012) Application of the world health organization criteria to predict radiographic pneumonia in a US-based pediatric emergency department. Pediatr Infect Dis J 31(6):561–564. doi: 10.1097/INF.0b013e31824da716 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Are Stuwitz Berg
    • 1
    • 2
  • Christopher Stephen Inchley
    • 1
  • Hans Olav Fjaerli
    • 1
  • Truls Michael Leegaard
    • 3
    • 2
  • Morten Lindbaek
    • 4
  • Britt Nakstad
    • 1
    • 2
  1. 1.Department of Pediatric and Adolescent MedicineAkershus University HospitalLørenskogNorway
  2. 2.Institute of Clinical Medicine, Faculty of MedicineUniversity of OsloOsloNorway
  3. 3.Department of Microbiology and Infection ControlAkershus University HospitalLørenskogNorway
  4. 4.Institute of Health and Society, Faculty of MedicineUniversity of OsloOsloNorway

Personalised recommendations