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Paediatrica Indonesiana

VOLUME 52 January  NUMBER 1

Original Article

Correlation between C-reactive protein and serum


iron levels in children with pneumonia
I Gd. Oka Novi Purnawan1, Ida Bagus Subanada1, Sri Mulatsih2

3
Abstract neumonia is an infectious disease that often
Background 3QHXPRQLDLVDQLQIHFWLRXVGLVHDVHRIWHQRFFXULQJ RFFXUVLQFKLOGUHQXQGHUILYH\HDUVRIDJH,Q
LQ FKLOGUHQ XQGHU ILYH \HDUV RI DJH $W WKH WLPH RI LQIHFWLRQ GHYHORSLQJ FRXQWULHV SQHXPRQLD FDXVHV D
pro-inflammatory cytokines are released. It is thought that these high morbidity and mortality rates.1 'XULQJ
pro-inflammatory cytokines cause changes to iron homeostasis
in the body.
infection, cytokines such as pro-inflammatory
Objective 7RGHWHUPLQHDFRUUHODWLRQEHWZHHQ&53DQGVHUXP interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor
LURQOHYHOVLQFKLOGUHQZLWKSQHXPRQLD necrotizing factor-D (TNF-D) are released. It is
Methods An analytical, cross-sectional study was performed thought that these pro-inflammatory cytokines may
LQ FKLOGUHQ DJHG  PRQWKV \HDUV ZLWK VHYHUH SQHXPRQLD DW lead to a change in iron homeostasis in the body.
6DQJODK +RVSLWDO 'HQSDVDU %DOL IURP $SULO1RYHPEHU 
Acute phase proteins, as products of pro-inflammatory
/DERUDWRU\ H[DPLQDWLRQV LQFOXGHG &53 DQG VHUXP LURQ OHYHOV
7KHFRUUHODWLRQEHWZHHQ&53DQGVHUXPLURQOHYHOVZDVDQDO\]HG F\WRNLQHUHOHDVHDUHRIWHQHYDOXDWHGDVDQLQGLUHFW
E\3HDUVRQVFRUUHODWLRQ measure for these cytokines.
Results)URPFKLOGUHQZLWKVHYHUHSQHXPRQLDFKLOGUHQ 'XULQJ DFXWH LQIHFWLRQV &UHDFWLYH SURWHLQ
IXOILOOHGWKHLQFOXVLRQFULWHULD6XEMHFWVPHGLDQ&53OHYHOZDV &53 DQDFXWHSKDVHSURWHLQLQFUHDVHVLQFRQFHQ
PJ/DQGPHGLDQ VHUXPLURQ OHYHOZDV  XJG/7KH
tration in the blood as a non-specific immune
FRHIILFLHQWFRUUHODWLRQEHWZHHQ&53DQGVHUXPLURQOHYHOVZDV
 3   7KH GHWHUPLQDWLRQ FRHIILFLHQW YDOXH ZDV UHVSRQVH,QGXFWLRQRI&53V\QWKHVLVLVWULJJHUHGE\
 cytokines, especially IL-6, that are released in areas
Conclusion ,Q FKLOGUHQ ZLWK VHYHUH SQHXPRQLD &53 OHYHO RI LQIODPPDWLRQ /DERUDWRU\ H[DPLQDWLRQ RI &53
FRUUHODWHVQHJDWLYHO\ZLWKVHUXPLURQOHYHOV[Paediatr Indones. concentration is often performed in patients with
2012;52:38-42].
pneumonia.4
Keywords: CRP, serum iron, pneumonia

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+HDOWK0HGLFDO6FKRRO*DGMDK0DGD8QLYHUVLW\'U6DUGMLWR+RVSLWDO
Yogyakarta, Indonesia.2

Reprint requests to:,*G2ND1RYL3XUQDZDQ'HSDUWPHQWRI&KLOG


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(PDLOgedeokanovi@yahoo.com

38Paediatr Indones, Vol. 52, No. 1, January 2012


I Gd. Oka Novi Purnawan et al: &UHDFWLYHSURWHLQDQGVHUXPLURQOHYHOVLQFKLOGUHQZLWKSQHXPRQLD

,Q 6HUELD 1DVWDVLMHYLF et al. 5 found iron DQG WKH 3XOPRQRORJ\ 'LYLVLRQ 'HSDUWPHQW RI
deficiency in adult patients suffering from community- &KLOG+HDOWK8GD\DQD8QLYHUVLW\0HGLFDO6FKRRO
DFTXLUHGSQHXPRQLD7KHLUVHUXPLURQOHYHOVVKRZHG 6DQJODK+RVSLWDO'HQSDVDU9HQRXVEORRGVSHFLPHQV
VLJQLILFDQW LPSURYHPHQW DIWHU  GD\V RI WKHUDS\ IRU FRPSOHWH EORRG FRXQWV &53 DQG VHUXP LURQ
despite the absence of iron supplementation, and examinations were collected at the time patients
&53 OHYHOV FRUUHODWHG QHJDWLYHO\ ZLWK VHUXP LURQ ZHUHGLDJQRVHGZLWKVHYHUHSQHXPRQLD6HUXPLURQ
OHYHOV7KHUHKDYHEHHQIHZVLPLODUVWXGLHVSHUIRUPHG concentration was measured by Beckman Coulter
in children. The aim of our study was to determine &;XVLQJVSHFWURSKRWRPHWU\&53FRQFHQWUDWLRQ
LIWKHUHLVDFRUUHODWLRQEHWZHHQ&53DQGVHUXPLURQ ZDVPHDVXUHGE\&2%$6,17(*5$6WDWLVWLFDO
OHYHOVLQFKLOGUHQZLWKSQHXPRQLD DQDO\VHV ZHUH SHUIRUPHG XVLQJ 6336  YHUVLRQ
IRU ZLQGRZV 3HDUVRQV FRUUHODWLRQ ZDV XVHG WR
DQDO\]H WKH DVVRFLDWLRQ EHWZHHQ &53 DQG VHUXP
Methods LURQOHYHOV

This cross-sectional, analytical study was conducted


DWWKH3XOPRQRORJ\'LYLVLRQ'HSDUWPHQWRI&KLOG Results
+HDOWK8GD\DQD8QLYHUVLW\0HGLFDO6FKRRO6DQJODK
+RVSLWDO%DOLIURP$SULOWR1RYHPEHU 'XULQJ WKH VWXG\ SHULRG RI WKH  FKLOGUHQ ZLWK
The number of required subjects was calculated SQHXPRQLDFKLOGUHQZHUHLQFOXGHGLQRXUVWXG\
using the single correlation test sample. We included Among the excluded 46 children, 5 children had
 VXEMHFWV ZLWK VHYHUH SQHXPRQLD DJHG  PRQWKV YHU\ VHYHUH SQHXPRQLD  FKLOGUHQ KDG DQHPLD
\HDUV:HH[FOXGHGSDWLHQWVZLWK YHU\VHYHUH KHPRJORELQ  JG/   FKLOGUHQ KDG D KLVWRU\
SQHXPRQLDRUVHYHUHSQHXPRQLDZLWKFRQFRPLWDQW of preterm birth and low birth weight, and 11
systemic diseases, post-surgery and burns; 2) a children had other systemic diseases (4 children with
history of preterm birth, low birth weight, and twin FRQJHQLWDOKHDUWGLVHDVHFKLOGZLWKOLYHUGLVHDVH
SUHJQDQFLHV IRRGDEVRUSWLRQSUREOHPV DQHPLD 1 child with a malignancy, 2 children with brain
SUHYLRXVLURQWKHUDS\ LQFRPSOHWHGDWDDQG ODFN infections, 1 child with post-laparotomy surgery, and
RISDUHQWJXDUGLDQFRQVHQW7KLVVWXG\ZDVDSSURYHG 2 children with sepsis).
by the Research Ethics Committee of Sanglah 7KH PHGLDQ FRQFHQWUDWLRQ RI &53 ZDV 
+RVSLWDO'HQSDVDU PJ/ UDQJHWR DQGWKHPHGLDQVHUXPLURQ
Clinical examinations were performed by FRQFHQWUDWLRQZDVJG/ UDQJHWR 
doctors in the emergency unit, outpatient ward, as shown in Table 1.

Table 1. Basic characteristics of subjects


Subject characteristics n = 23
Median age, months (minimum-maximum) 13.0 (6.0-58.0)
Sex
Male 13
Nutritional status
Well-nourished 10
Undernourished 8
Overweight 5
#VTKUMQHKTQPFGEKGPE[FWGVQFKGV 23
Median laboratory parameters, (minimum-maximum)
Hemoglobin,g/dL 11.8 (11-13.9)
WBC, x103 /L 11.2 (6.09-29.2)
Absolute neutrophil, x103 /L 5.74 (1.82-20.8)
CRP, mg/L 9.22 (0.22-53.5)
Iron serum, g/dL 25.55 (9.13-76.46)
Median time of CRP and serum iron measurement 4.0 (2.0-7.0)
after symptom onset, days (minimum-maximum)

Paediatr Indones, Vol. 52, No. 1, January 2012 39


I Gd. Oka Novi Purnawan et al: &UHDFWLYHSURWHLQDQGVHUXPLURQOHYHOVLQFKLOGUHQZLWKSQHXPRQLD

Observed
80.00 Quadratic

Serum iron level (ug/dL)


60.00

40.00

R Square line = 0.316

20.00

0.00
0.00 10.00 20.00 30.00 40.00 50.00 60.00

CRP level (mg/L)

Figure 1. Scatter plot correlation of CRP and serum iron levels in children with severe
pneumonia.

7KH 6KDSLUR:LON WHVW UHYHDOHG DEQRUPDO LQYLUDOLQIHFWLRQVVXFKDVLQIOXHQ]D$DQGLQIOXHQ]D


GDWD GLVWULEXWLRQ LQ &53 DQG VHUXP LURQ OHYHOV 7R %ZLWK&53OHYHOVUDQJLQJEHWZHHQPJ/
normalize this data distribution, we performed data 2WKHUVWXGLHVUHSRUWHGHOHYDWHGOHYHOVRI&53!
WUDQVIRUPDWLRQ XVLQJ WKH ORJ PHWKRG 3HDUVRQV mg/L in cases of pneumonia accompanied by empyema
FRUUHODWLRQ WHVW UHYHDOHG D ZHDN EXW VWDWLVWLFDOO\ DQG QHFURWL]LQJ SQHXPRQLD ZKLOH DYHUDJH &53
VLJQLILFDQW QHJDWLYH FRUUHODWLRQ EHWZHHQ &53 DQG FRQFHQWUDWLRQV LQ DGHQRYLUXV LQIHFWLRQV FDQ UHDFK
VHUXP LURQ OHYHOV U   3    ,I &53 PJ/
OHYHOV LQFUHDVHG VHUXP LURQ OHYHOV GHFUHDVHG DQG ,QRXUVWXG\WKHPHGLDQ&53FRQFHQWUDWLRQZDV
YLFHYHUVD PJ/UDQJLQJIURPPJ/VLPLODUWR
7KHUHODWLRQVKLSEHWZHHQ&53DQGVHUXPLURQ WKDWRISUHYLRXVVWXGLHV7KHVH&53OHYHOVVXJJHVW
OHYHOVLVVKRZQLQFigure 1. Scatter plots showed that that the cause of pneumonia in most of our subjects
WKHUHODWLRQVKLSEHWZHHQ&53DQGVHUXPLURQOHYHOV ZDVYLUDO/RZ&53OHYHOVDUHDOVROLNHO\WREHGHWHFWHG
was non-linear. The quadratic model was statistically LI&53H[DPLQDWLRQLVSHUIRUPHGDIWHUWKHVXEMHFWKDV
VLJQLILFDQW ) GI 3  DQGPRUH SDVVHGWKHSHDNLQFUHDVHVWDJHRI&537KHDYHUDJH
precise than linear model. Scatter plot also showed &53H[DPLQDWLRQWLPHLQRXUVWXG\ZDVGD\VDIWHU
WKH QHJDWLYH UHODWLRQVKLS EHWZHHQ &53 DQG VHUXP RQVHWRILQLWLDOSQHXPRQLDV\PSWRPVVXFKDVIHYHU
LURQOHYHOVLQFKLOGUHQZLWKVHYHUHSQHXPRQLD7KH FRXJKDQGUXQQ\QRVH,QWKHRU\&53OHYHOVUHDFKWKH
GHWHUPLQDWLRQFRHIILFLHQWYDOXHZDV ORZHVWYDOXHDWGD\VDQGDIWHUVWLPXODWLRQ12
The inflammatory process may disrupt iron
homeostasis. Impaired iron homeostasis begins
Discussion with increased uptake and retention of iron in
reticuloendothelial cells. Iron from the circulation is
In pneumonia patients, infection and tissue damage stored in the reticuloendothelial system, where its use
in the lung parenchyma may stimulate the immune is limited to stem cell erythropoiesis. Stimulation of
V\VWHPWRUHOHDVH&53LQWRWKHEORRGVWUHDP,QFUHDVHG pro-inflammatory cytokines (TNF-D, IL-1, IL-6) leads
&53OHYHOVDUHRIWHQVHHQLQFDVHVRISQHXPRQLDGXH to the retention of iron in macrophages. Furthermore,
WREDFWHULDOLQIHFWLRQ+HQFH&53WHVWLQJLVXVHIXO down-regulation of ferroportin production withholds
to distinguish bacterial infections from other causes the release of ferrous iron from duodenum enterocytes
RILQIHFWLRQV,QFUHDVHG&53OHYHOVFDQDOVREHIRXQG into the circulation. Kemna et al. found that after

40Paediatr Indones, Vol. 52, No. 1, January 2012


I Gd. Oka Novi Purnawan et al: &UHDFWLYHSURWHLQDQGVHUXPLURQOHYHOVLQFKLOGUHQZLWKSQHXPRQLD

humans were injected with lipopolysaccharide, serum strength. This difference may be due to different
LURQOHYHOVJUDGXDOO\GHFUHDVHGHVSHFLDOO\LQWKHILUVW etiologies of pneumonia. In Serbia, most infections
KRXUVDQGUHDFKHGWKHORZHVWOHYHODIWHUKRXUV were bacterial, while most infections in our study
The median serum iron concentration of in our ZHUH OLNHO\ WR EH YLUDO $ OLPLWDWLRQ RI RXU VWXG\ LV
VXEMHFWVZDVJG/UDQJLQJIURP WKDWZHGLGQRWSHUIRUPYLUXVLVRODWLRQVRUSRO\PHUDVH
g/dL, lower than that of a Serbian study which FKDLQUHDFWLRQ 3&5 WHVWVWRGHWHUPLQHSQHXPRQLD
UHSRUWHGDPHDQVHUXPLURQOHYHOLQDGXOWSQHXPRQLD etiology. We only performed blood cultures, not lung
SDWLHQWVRIPRO/ J tissue or pleural fluid. Blood cultures were sterile
dL).5 This difference may be due to subjects age for all subjects. Blood culture results do not rule
GLIIHUHQFHV7KHPHGLDQDJHRIRXUVXEMHFWVZDV out the possibility that bacteria caused our subjects
PRQWKVDQDJHYXOQHUDEOHWRLURQGHILFLHQF\14 while pneumonia, since there is generally a low incidence
the Serbian subjects were adults.5 of bacteremia during pneumonia.
A study of serum iron profiles reported mean Another limitation of our research was that
VHUXP LURQ FRQFHQWUDWLRQV LQ FKLOGUHQ ZLWK VHYHUH &53DQGVHUXPLURQOHYHOVZHUHQRWPHDVXUHGDIWHU
PDOQXWULWLRQ WR EH    JG/ LQ VHYHUHO\ initiation of therapy. So we do not know if serum
malnourished children with no acute respiratory iron spontaneously increased after therapy. Since the
LQIHFWLRQWREHJG/DQGLQVHYHUHO\ WHVWLQJ WLPHV RI &53 DQG VHUXP LURQ OHYHOV YDULHG
malnourished children with acute respiratory infection the data distribution was abnormal. Also, we did
WREHJG/15 All of their results were QRWDFFRXQWIRUWKHLQIOXHQFHRIGLXUQDOYDULDWLRQRQ
higher than that in our study (25.55 g/dL). This VHUXPLURQOHYHOV)XUWKHUPRUHDOOVXEMHFWVZHUHDWULVN
GLIIHUHQFHPD\EHGXHWROHVVVHYHUHDFXWHUHVSLUDWRU\ for iron deficiency due to their dietary status. Since
infections in their study (upper acute respiratory serum ferritin was not examined in our study, we do
infections), compared to acute lower respiratory QRWNQRZLIWKHORZVHUXPLURQOHYHOVLQRXUVXEMHFWV
infections in our study.15 were caused by infection alone, or influenced by low
Iron homeostasis disruption occurs during the LURQUHVHUYHV
inflammatory process. In our study, we determined ,Q FRQFOXVLRQ &53 OHYHO ZDV QHJDWLYHO\
WKH GHJUHH RI LQIODPPDWLRQ E\ PHDVXULQJ &53 FRUUHODWHG ZLWK VHUXP LURQ OHYHO LQ FKLOGUHQ ZLWK
OHYHOVDVDQHQGUHVXOWRISURLQIODPPDWRU\F\WRNLQH VHYHUH SQHXPRQLD )XUWKHU UHVHDUFK LV QHHGHG WR
stimulation, especially IL-6. We determined iron HYDOXDWHLURQVWDWXVLQFOXGLQJIHUULWLQH[DPLQDWLRQV
KRPHRVWDVLVGLVUXSWLRQE\PHDVXULQJVHUXPLURQOHYHOV LQRUGHUWRSURYLGHPRUHVSHFLILFLQIRUPDWLRQRQWKH
:HIRXQGDQHJDWLYHFRUUHODWLRQEHWZHHQ&53DQG impact of lower respiratory tract infection on iron
VHUXPLURQOHYHOVLQFKLOGUHQZLWKVHYHUHSQHXPRQLD metabolism.
7KHFRUUHODWLRQFRHIILFLHQWZDV 3  
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with pneumonia correlated to decreased serum iron Acknowledgments
OHYHOV7KHVHUHVXOWVZHUHFRQVLVWHQWZLWKD6HUELDQ
VWXG\ZKLFKVKRZHGWKDWVHUXPLURQOHYHOVQHJDWLYHO\ :H DUH GHHSO\ JUDWHIXO WR , *GH 5DND :LGLDQD 0' DQG ,%
FRUUHODWHGZLWK&53OHYHOV U 3 5 6XEDQDGD0'IRUWKHLUKHOSLQFRQVWUXFWLQJPHWKRGRORJ\DQG
7KHUH ZDV D SRVLWLYH UHODWLRQVKLS EHWZHHQ statistical analysis in this study.
&53DQGVHUXPLURQOHYHOVDIWHU&53FRQFHQWUDWLRQ
H[FHHGHG  PJ/ DV VKRZQ E\ WKH DVFHQGLQJ
TXDGUDWLFOLQH7KLVFRQGLWLRQPD\KDYHEHHQGXHWR References
YDU\LQJWLPHVRI&53DQGVHUXPLURQWHVWLQJ7KHPRVW
rapid examination was at 2 days and the least was at  %U\FH - %RVFKL3LQWR & 6KLEX\D . %ODFN 5( :+2
GD\VDIWHUSUHVHQWDWLRQRIHDUO\FOLQLFDOV\PSWRPV estimates of the causes of death in children. Lancet.
of pneumonia. 
We found the correlation strength to be weaker  :DOWHU72OLYDUHV03L]DUUR)0XQRV&,URQDQHPLDDQG
than that of the Serbian study, which was of medium LQIHFWLRQ1XWU5HY 

Paediatr Indones, Vol. 52, No. 1, January 2012 41


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4. Kratz A, Lewandrowski EL. The plasma protein. In: Kenneth /XQJ,QGLD
'0HGLWRU&OLQLFDOODERUDWRU\PHGLFLQHndHG3KLODGHOSKLD  $OPLUDOO-%ROLEDU,7RUDQ33HUD*%RTXHW;%DODQ]R;
/LSSLQFRWW:LOOLDPV :LONLQVS HWDO&RQWULEXWLRQRI&UHDFWLYHSURWHLQWRWKHGLDJQRVLV
 1DVWDVLMHYLF'%3HMFLF75DGMHQRYLF75DGRYLF0,QYHUVH DQG DVVHVVPHQW RI VHYHULW\ RI FRPPXQLW\DFTXLUHG
FRUUHODWLRQRI&53DQGVHUXPLURQLQSDWLHQWVZLWKVLPSOH pneumonia, for the community-acquired pneumonia. Chest.
FRPPXQLW\DFTXLUHG SQHXPRQLD &$3  $FWD )DF 0HG 
1$,66  *DED\&.XVKQHU,$FXWHSKDVHSURWHLQDQGRWKHUV\VWHPLF
 /XQD&0&UHDFWLYHSURWHLQLQSQHXPRQLDOHWPHWU\DJDLQ UHVSRQVHVWRLQIODPPDWLRQ1(QJO-0HG
&KHVW  .HPQD(3LFNNHUV31HPHWK(YDQGHU+RHYHQ+6ZLQNHOV
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 /LQ &- &KHQ 3< +XDQJ )/ /HH 7 &KL &6 /LQ &< 
Radiographic, clinical, and prognostic features of complicated  %URWDQHN-0*RV]-:HLW]PDQ0)ORUHV*,URQGHILFLHQF\
and uncomplicated community-acquired lobar pneumonia in in early childhood in the United States: risk factors and racial/
FKLOGUHQ-0LFURELRO HWKQLFGLVSDULWLHV3HGLDWULFV
 )DUQJ.7:X.*/HH<6/LQ<++ZDQJ%7&RPSDULVRQ 15. Rahman MA, Mannan MA, Rahman MH, Aretin KE, Azad
RIFOLQLFDOFKDUDFWHULVWLFVRIDGHQRYLUXVDQGQRQDGHQRYLUXV AK. Influence of acute respiratory infection on iron profile
pneumonia in children. J Microbiol Immunol Infect. LQ VHYHUHO\ PDOQRXULVKHG FKLOGUHQ 0\PHQVLQJK 0HG -
 6

42Paediatr Indones, Vol. 52, No. 1, January 2012

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