Journal of Tropical Pediatrics, 2020, 66, 419–427

doi: 10.1093/tropej/fmz082
Advance Access Publication Date: 10 December 2019
Original paper

Efficacy of Adjunctive Zinc in Improving

the Treatment Outcomes in Hospitalized
Children with Pneumonia: A Randomized

Downloaded from https://academic.oup.com/tropej/article/66/4/419/5671781 by guest on 08 November 2024

Controlled Trial
Lakkana Rerksuppaphol, MD1 and Sanguansak Rerksuppaphol, MD2
1
Department of Preventive Medicine, Srinakharinwirot University, Nakorn Nayok 26120, Thailand
2
Department of Pediatrics, Faculty of Medicine, Srinakharinwirot University, Nakorn Nayok 26120, Thailand
Correspondence: Sanguansak Rerksuppaphol, Department of Pediatrics, Faculty of Medicine, Srinakhariwirot University, 62 Mo 7, Rangsit-
Nakorn Nayok Rd., Nakorn Nayok 26120, Thailand. Tel: 668-1723-1766. Fax: 663-7395275. E-mail <sanguansak_r@hotmail.com>.

ABSTRACT

Background: The mortality rate of pneumonia is high, placing a huge burden on developing coun-
tries. Healthcare professionals use zinc as an adjunctive treatment for children with pneumonia;
however, this contradicts with some published reports. Thus, this study aimed to assess the efficacy
of zinc supplementation on the treatment outcomes of pneumonia.
Methods: A randomized, double-blind, placebo-controlled trial was conducted on hospitalized chil-
dren with pneumonia. The children randomly received either zinc bis-glycinate (15 mg elemental
zinc) or placebo, twice per day. The primary outcome was the resolution time of pneumonia, and
the secondary outcomes were the duration of hospitalization and the recovery times of each clinical
symptom.
Results: Out of the 91 children, 65 (71.4%) were males. The resolution period of clinical pneumo-
nia was significantly shorter in the zinc group than the placebo group (48 and 72 h, respectively; haz-
ard ratio ¼ 0.585, 95% confidence interval 0.377–0.908). Similarly, the hospitalization period and
the resolution period of fever were shorter in the zinc group [96 and 144 h (p ¼ 0.008), and 24 and
42 h (p ¼ 0.002), respectively]. Children receiving zinc needed a median of 28 h to reach the normal
level of oxygen saturation compared to 48 h required by children under placebo (p ¼ 0.014).
Conclusion: Zinc supplementation enhanced the treatment outcomes of pneumonia, by reducing
the resolution period of pneumonia and normalizing oxygen levels and body temperature. The
length of hospital stay for children receiving zinc was shorter than those receiving placebo.

K E Y W O R D S : dietary supplements, pneumonia, zinc

INTRODUCTION chest indrawing, nasal flaring and a depressed level

Pneumonia is a serious inflammatory condition of consciousness [1]. A higher incidence has been
caused by bacterial or viral pathogens. According to reported in low-middle income nations, compared to
the World Health Organization (WHO), signs and high-income nations, with 0.22 and 0.05 episodes
symptoms of pneumonia in children include breath- per child-year (e/cy), respectively [1]. In 2015,
ing difficulties, coughing, a rapid respiratory rate, pneumonia was responsible for the death of 920 000

C The Author(s) [2019]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com
V  419
420  Zinc Supplementation for Pneumonia

children under the age of 5 years, which represented symptoms in children. The trial took place from
19% of the childhood mortality rate in the world at June 2018 to March 2019 at the Pediatric
that time, with the rate being highest in South Asian Department of Srinakharinwirot University Hospital,
and sub-Saharan African children [2]. Thailand. The study was registered at the Thai
Antimicrobial drugs, analgesics, antipyretics and Clinical Trials Registry (TCTR20190220001) and
fluids are typically effective in the resolution of pneu- the Ethics Committee of Srinakharinwirot University
monia [3]. However, prevention measures, including approved the study protocol. Written informed con-
immunization, balanced diet, breastfeeding and the sent was obtained from the parents or legal guardians
proper management of other health disorders, ameli- of eligible children before participation.

Downloaded from https://academic.oup.com/tropej/article/66/4/419/5671781 by guest on 08 November 2024

orate the treatment outcomes [4]. Recent research
studies have explored the role of malnutrition as a Participants
possible risk factor for respiratory tract infections Children between the ages of 2 and 60 months, who
and pneumonia [5]. Zinc is an essential nutritional were admitted to hospital with pneumonia, were eli-
element for growth and for boosting the immune gible to participate in this trial. Their diagnosis of
system. Children in developing countries are more li- pneumonia was defined on the basis of the WHO
able to suffer from zinc deficiency because of inad- classification, namely: children with fast breathing
equate nutrition, as well as zinc excretion following (respiratory rate 50 breaths/min in children
frequent diarrhea [6, 7], and it has been estimated <12 months of age, or 40 breaths/min in children
that around 40% of Thai people are at risk of zinc 12 months of age) and/or chest indrawing [13].
deficiency due to insufficient intake [6]. Physicians Exclusion criteria were: (i) children with major con-
have been administering zinc to children with pneu- genital anomalies, (ii) chronic medical conditions,
monia as an adjunctive remedy; however, contradict- such as chronic liver or renal diseases, immune defi-
ory results have been reported. For instance, the trial ciency or malignancy and (iii) children with respira-
conducted by Valavi et al. [8] deduced that zinc has tory or cardiovascular failure and those who needed
enhanced the recovery from pneumonia and has mechanical ventilation support or inotropic
shortened the length of the hospital stay. Moreover, medications.
another trial revealed that zinc decreased the reso-
lution period of pneumonia, as well as the hospital- Randomization and intervention
ization period [9]. In contrast, some trials did not The enrolled children were randomly allocated in a
show a significant reduction in the resolution 1:1 ratio to receive either zinc or placebo, by a com-
period of pneumonia or the length of the hospital puterized program (GraphPad QuickCalcs) using a
stay [10–12]. block of four by an independent investigator. The in-
Given these controversial findings, we aimed to vestigator, attending physicians, children and parents
carry out a randomized, double-blind, placebo-con- were masked to the intervention. The randomization
trolled trial to investigate the role of zinc in shorten- sequence was opened only after the study comple-
ing the recovery period from pneumonia symptoms tion and the data was stored and analyzed anonym-
and the length of the hospitalization period. To the ously, using encryption codes.
best of our knowledge, this is the first randomized Regarding the trial, each child received a single-
trial in Thailand that examines the efficacy and toler- dose twice per day of either 15 mg elemental zinc, in
ance of zinc in children with pneumonia. the form of zinc bis-glycinate powder, or placebo,
dissolved in 30 ml distilled water, until their
discharge from the hospital, or the completion of
METHODS
7 days. Zinc bis-glycinate and placebo (dextrose
Design and ethics monohydrate) were prepared in powder form in a
A randomized, double-blind, placebo-controlled trial single-dose sachet by a pharmaceutical company
was carried out to examine the efficacy of zinc sup- (Qualimed, Bangkok, Thailand). The drug and pla-
plementation in the recovery from pneumonia cebo were indistinguishable in their color, taste and
 Zinc Supplementation for Pneumonia  421

appearance. They were both purchased from the respiratory distress, fever, as well as the adjustment
same manufacturing company, which played no role of SpO2 and oral feeding.
in the design, data analysis, data interpretation of the
study or the publication process. Outcome measures
The primary outcome of this trial was the length of
Data collection and follow-up the resolution period of pneumonia, which is defined
The basic demographic data and detailed history of as the period from the participants’ enrollment to
present illness were collected from all children at the their recovery from tachypnea, chest indrawing, hyp-
oxemia and fever, for at least 12 h. The secondary

Downloaded from https://academic.oup.com/tropej/article/66/4/419/5671781 by guest on 08 November 2024

time of enrollment. Blood samplings were collected,
using trace element-free vacutainers and storage outcomes were the duration of hospitalization and
tubes, to measure the serum zinc and to perform a the recovery time of each clinical symptom.
complete blood count. All the included children
were physically examined and treated per standard Sample size
protocol for pneumonia by the attending physicians. The sample size was estimated with regard to a
The clinical condition of the children was re-assessed mean resolution time of pneumonia of 47.5 h [8], a
by the same physician every 4 h. The respiratory rate 10% effect size, a 5% chance of a Type I error and a
was estimated by counting the respiratory chest 20% chance of a Type II error. Accordingly, we
movements per minute when children were calm. aimed to enroll at least 40 pneumonia cases in each
Tachypnea was defined as breathing that was faster group. A total of 96 patients were considered, with
than the normal rate, depending on their age (re- an estimated drop-out rate of 20%.
spiratory rate 50 breaths/min in children
Statistical analysis
<12 months of age, or 40 breaths/min in children
The statistical analysis was performed by using IBM
12 months of age). Nasal flaring and chest indraw-
SPSS Statistics 23.0 (IBM Crop., Armonk, NY,
ing were also assessed. Oxygen saturation (SpO2)
USA). Continuous variables were expressed as a
was measured by a pulse oximeter every 4 h and a
mean and standard deviation or as a median and
SpO2 of <95% was classified as hypoxemia. For
interquartile range (25th–75th percentile). A com-
patients receiving oxygen therapy, the oxygen supply parison between the placebo and control groups was
was discontinued for 2 min to assess the respiratory carried out by using the Student’s t-test and the
rate, chest indrawing and oxygen saturation. The ax- Mann–Whitney U-test. Proportions were compared
illary temperature was measured every 4 h by using a by using the Pearson v2 test or the Fisher’s exact
standard mercury thermometer, and a temperature test. Cox proportional regression models were
of 37.8 C, or above, was defined as a fever. Recovery employed to compare the time of symptoms’ cessa-
from fever and hypoxemia for two sequential assess- tion between the two groups, by calculating the haz-
ments entailed the normalization of the temperature ard ratio (HR). A two-way analysis of variance was
and SpO2. Resolution of pneumonia is defined as the performed to assess the effect of zinc supplementa-
period starting from enrollment to the disappearance tion and the baseline zinc status on the remission of
tachypnea, chest indrawing, hypoxemia and fever, for the disease. All p-values <0.05 were considered to
at least 12 h. Baseline serum zinc levels were esti- be statistically significant.
mated by flame atomic absorption spectrometry. A
zinc deficiency was recognized if the serum zinc con- RESULTS
centration was <65 mg/dl [14]. We checked for ad- A total of 98 children, aged between 2 and
verse events in both the treatment and control 60 months met the inclusion criteria. The parents of
groups by using open-ended questions. Therapeutic seven children refused to participate. Thus, the
compliance was evaluated by the sum of the supple- remaining 91 cases were randomly assigned: 46 sub-
ment intake. Physicians decided to discharge some jects were allocated to receive zinc, while 45 cases
patients, owing to their resolution of tachypnea, were allocated to the placebo group. None of the
422  Zinc Supplementation for Pneumonia

patients discontinued the treatment or failed to group and one child in the placebo group experi-
follow-up. A flow chart of the enrollment process enced nausea/vomiting, while one child in each
and procedures is shown in Fig. 1. group also had loose stools during the study period.
Of the 91 children, 65 (71.4%) were male and the All the symptoms spontaneously resolved in a few
median (interquartile range) age was 19 (13–33) days, without applying treatment.
months. There were no significant differences in
baseline characteristics and clinical presentations at DISCUSSION
the enrollment including body temperature, respira- In this study, we presented a randomized, double-
tory rate, pulse, oxygen saturation, nasal flaring and blind, placebo-controlled study on the efficacy of

Downloaded from https://academic.oup.com/tropej/article/66/4/419/5671781 by guest on 08 November 2024

chest indrawing between the zinc and the placebo zinc supplementation, as an adjuvant therapy, in chil-
group. Baseline serum zinc concentration and the dren with pneumonia. The study was conducted in
prevalence of zinc deficiency were compared be- Thailand, where around 40% of the population are at
tween the two study groups (Table 1). risk of zinc deficiency due to inadequate intake [6].
Upon completion of the trial, the median reso- It was found that zinc was a tolerable supplement
lution period of pneumonia was significantly shorter that showed a significant effect on shortening the
in the zinc group compared to the placebo group resolution period of pneumonia, fever and the dur-
(48 and 72 h, respectively; HR ¼ 0.585, 95% confi- ation of hospitalization. The time needed to normal-
dence interval 0.377–0.908) (Table 2). Similarly, the ize oxygen saturation levels was markedly lowered in
time needed for normalizing oxygen saturation level, subjects receiving zinc, compared to the placebo
resolution of fever and the length of hospital stay group, but it showed no difference in regard to the
were significantly shorter in the zinc group compared remission of tachypnea and chest indrawing. The
to the placebo group. However, the resolution period baseline zinc status did not manipulate the trial
of tachypnea and chest indrawing were not signifi- results, including the remission of tachypnea, chest
cantly different between the two study groups indrawing and hypoxemia.
(Table 2). After 5 days of therapy, four (8.7%) chil- In the light of the findings of our trial, previously
dren in the zinc group and seven (15.6%) children in published studies in the literature revealed both har-
the placebo group showed persistent signs of pneu- monious and conflicting results. In 2014,
monia (p ¼ 0.354). By the seventh day of therapy, Qasemzadeh et al. [15] deduced that zinc supple-
none of the children in the zinc group had persistent mentation (5 ml every 12 h) shortened the hospital-
signs of pneumonia, compared to three (6.7%) chil- ization period and remission of the clinical
dren in the placebo group (p ¼ 0.117). symptoms of pneumonia among Iranian children,
A two-way analysis of variance showed that the aged between 3 and 60 months. The following year,
baseline zinc status did not affect the remission of another trial was conducted among Pakistanis chil-
tachypnea (p ¼ 0.104), chest indrawing (p ¼ 0.056) dren, aged between 2 and 23 months, which indi-
and hypoxemia (p ¼ 0.102). However, zinc supple- cated that zinc syrup (20 mg/day) can lessen the
mentation had significant effect on the remission severity of pneumonia and shorten the hospitaliza-
duration of hypoxemia (p ¼ 0.016), but showed no tion period [16]. In a recent randomized trial in
significant effects on the remission duration of tach- Gambia, zinc was proven to reduce the resolution
ypnea (p ¼ 0.078) and chest indrawing (p ¼ 0.068). time of chest indrawing and sternal retraction; how-
The interaction effects between the baseline zinc sta- ever, it showed no benefit in treatment failure rates.
tus and zinc supplementation had no effect on the The children were aged between 2 and 59 months
remission duration of all pneumonia signs, namely, and the treatment group received 10 mg/day of zinc
tachypnea (p ¼ 0.473), chest indrawing (p ¼ 0.872) sulfate for 7 days [17].
and hypoxemia (p ¼ 0.261). In contrast, multiple randomized trials showed no
Throughout the trial period, none of the patients benefits of zinc supplementation for children with
died or had serious adverse events. All reported pneumonia. For instance, one study which was car-
events were tolerable; only two children in the zinc ried out among Ecuadorian children, aged between 2
 Zinc Supplementation for Pneumonia  423

Enrollment
Assessed for eligibility (n= 98)

Declined to participate (n= 7)

Downloaded from https://academic.oup.com/tropej/article/66/4/419/5671781 by guest on 08 November 2024

Randomized (n= 91)

Allocation
Zinc group (n= 46) Control group (n= 45)
♦Received allocated intervention (n= 46) ♦ Received allocated intervention (n= 45)

Follow-Up
Discontinued intervention (n= 0) Discontinued intervention (n= 0)

Analysis
Analyzed (n= 46) Analysed (n= 45)
♦Excluded from analysis (n= 0) ♦Excluded from analysis (n= 0)

Fig. 1. Study flow chart and enrollment.

and 59 months, concluded that zinc has no signifi- of zinc. The authors of the present research presume
cant benefit on the recovery period of pneumonia that the degree of disease severity, the different dos-
and the length of hospital stay. Interestingly, the ages of zinc, the area of research and the season in
authors observed that a higher baseline zinc status which the study was conducted may have been re-
was associated with more rapid resolution of chest sponsible for the varied results among the reported
indrawing, which is inconsistent with our study [11]. trials. Furthermore, certain studies did not specify
This may have been explained by the different popu- which zinc format was utilized [15, 16, 18]. The dif-
lation characteristics and the varied cutoff values of ferent forms of zinc may also explain the controver-
zinc deficiency in both trials. Similarly, the trial of sial findings between the published trials. The
Vinayak et al. [18] showed that zinc use didn’t bene- present trial, for instance, utilized chelated zinc,
fit the remission period of pneumonia and the length which has a higher bioavailability and absorption
of the hospitalization period. That study’s population than inorganic zinc [19]. In addition, different forms
was aged between 3 and 60 months and children in of organic zinc, such as bis-glycinate and zinc gluco-
the treatment arm were administered 10–20 mg/day nate, have varying degrees of absorption [20].
424  Zinc Supplementation for Pneumonia

Table 1. Baseline characteristics of the enrolled children in the zinc and placebo groups
Variables Placebo (n ¼ 45) Zinc (n ¼ 46) p-value

Male, n (%) 29 (64.4) 36 (78.2) 0.169

Age (months)a 17.0 (13.0–31.5) 19.5 (13.0–34.3) 0.512
Age group 0.603
2–11 months 9 (20.0) 9 (19.6)
12–23 months 20 (44.4) 18 (39.1)

Downloaded from https://academic.oup.com/tropej/article/66/4/419/5671781 by guest on 08 November 2024

24–35 months 6 (13.3) 9 (19.6)
36–47 months 7 (15.6) 4 (8.7)
48–60 months 3 (6.6) 5 (13.0)
Weight (kg) 10.6 (2.9) 12.1 (4.1) 0.056
Height (cm) 80.7 (15.2) 84.6 (14.7) 0.220
Clinical characteristics
Body temperature ( C) 38.4 (0.8) 38.3 (0.8) 0.599
Respiratory rate (breaths/min) 50 (5) 50 (6) 0.897
2–11 months 55 (4) 54 (4) 0.672
12–60 months 49 (4) 49 (6) 0.955
Pulse (beats/min) 168 (20) 1651 (16) 0.351
Oxygen saturation at room air (%) 95.1 (2.4) 94.6 (3.6) 0.759
Nasal flaring, n (%) 42 (93.3) 37 (80.4) 0.119
Chest indrawing, n (%) 43 (95.6) 44 (95.7) 1.000
Wheezing, n (%) 23 (51.1) 27 (58.7) 0.530
Hemoglobin (g/dl) 11.2 (1.5) 11.7 (1.2) 0.118
Leucocyte counta (103/mm3) 14.2 (10.1–19.5) 14.4 (11.2–16.6) 0.298
Neutrophil (%) 62.1 (16.4) 62.1 (18.7) 0.990
Platelets (103/mm3) 419.7 (135.6) 380.0 (122.8) 0.147
Zinc levels (lg/dl) 77.2 (21.8) 74.2(19.9) 0.481
Zinc deficiency, n (%) 16 (35.6) 16 (34.8) 1.000

Data were presented as a mean (standard deviation), unless otherwise indicated.

a
Presented as median (interquartile range).

It is worth mentioning that the quantitative meta- published meta-analysis of six trials (n ¼ 2216), it
analysis aims to build conclusive evidence regarding was shown that zinc is effective in reducing the mor-
the particular role of zinc as a supplemental treat- tality of severe pneumonia (p ¼ 0.01) and had a fa-
ment for children with pneumonia. The authors of vorable trend for clinical deterioration of severe
the first meta-analysis extracted the data of 2926 chil- pneumonia but with no statistical significance
dren who were younger than 5 years old, from nine (p ¼ 0.55). The analysis also showed that zinc had
randomized trials. When these trials were pooled no significant improvement of treatment failure
into a quantitative meta-analysis, the failure of zinc (p ¼ 0.71) and that the sub-group meta-analysis of
to reduce the recovery period from severe pneumo- the treatment duration >7 days did not affect the re-
nia (p ¼ 0.58), the length of hospitalization sult [22].
(p ¼ 0.74) and treatment failure (p ¼ 0.58) was It is worth noting that zinc deficiency can be cor-
revealed. This meta-analysis has been limited by the related with the risk of pneumonia infection. Zinc is
significant heterogeneity of the included studies and an essential antioxidant that has a cytoprotective dis-
the lack of a sub-group analysis [21]. In a recently- posal activity against toxins and the chemical
 Zinc Supplementation for Pneumonia  425

Table 2. Effect of zinc supplementation on recovery time by clinical indicators

Variables Median (IQR) Hazard ratioa (95% CI) p-value

Placebo (n ¼ 45) Zinc (n ¼ 46)

b
Time to resolution of pneumonia (h) 72 (48–96) 48 (45–72) 0.585 (0.377–0.908) 0.017
Time to disappearance of tachypneac (h) 60 (48–96) 48 (45–72) 0.704 (0.453–1.091) 0.117
Time to disappearance of chest indrawing (h) 48 (48–72) 48 (24–72) 0.730 (0.479–1.115) 0.145
Time to normalization of oxygen saturationd (h) 48 (36–72) 28 (24–48) 0.589 (0.383–0.897) 0.014

Downloaded from https://academic.oup.com/tropej/article/66/4/419/5671781 by guest on 08 November 2024

Time to resolution of fevere (h) 42 (24–72) 24 (12–36) 0.482 (0.307–0.757) 0.002
Hospitalization (h) 144 (88–168) 96 (72–120) 0.539 (0.342–0.850) 0.008
a
Hazard ratio for time until resolution of clinical pneumonia was estimated by using Cox proportional regression models. A value of <1 indicated the
beneficial effect of zinc supplementation.
b
Resolution of pneumonia defined as the period starting from enrollment to the disappearance tachypnea, chest indrawing, hypoxemia and fever, for at
least 12 h.
c
Disappearance of tachypnea defined as respiratory rate <50/min in aged 2–12 months or <40/min in children aged >12 months.
d
Normalization of oxygen saturation defined as oxygen saturation 95%.
e
Resolution of fever defined as axillary temperature lower than 37.8 C.

mediators of inflammation [23]. It can protect chil- the outcome of the trial and introduced a potential
dren against infection, especially respiratory infec- bias. However, the resolution of the clinical charac-
tions such as pneumonia, by enhancing the function teristics was defined as the primary endpoint. The
of T-lymphocytes and altering the immune- absorption of zinc can be affected by baseline zinc
modulators and immune regulators [24]. There is a status, dietary phytate and minerals. Phytate is an in-
growing understanding of the exact mechanism of gredient in multiple common foods that are con-
the anti-inflammatory and anti-oxidant functions of sumed by Thai people and it has a vigorously
zinc. Zinc significantly contributes to the signal negative impact on zinc absorption [29]. Although
transduction pathways and to the formation of neu- the children were advised not to take the trial’s rem-
trophil extracellular traps that bind to pathogens edies with their meals, and to avoid the intake of fur-
[25]. Furthermore, recent research has postulated ther vitamins and minerals, the study lacked dietary
that zinc targets Nuclear Factor Kappa B (NF-jB), protocols and rigorous oversight. This study has also
and hence, alters the pro-inflammatory response been limited by the small number of enrolled partici-
[26]. In a case–control study conducted by Arica pants, which may affect its generalizability and au-
et al., [27] children with pneumonia had a consider- thenticity on a global scale. Larger randomized trials
ably lower serum zinc concentration, compared to are recommended for future investigations, to exten-
the healthy control group. The present study found sively examine the efficacy of zinc as an adjunctive
that 35% of the participants had zinc deficiency on therapy for children with pneumonia. Various varia-
admission, and such a depressed level is consistent bles that may influence the outcomes should be con-
with the previously published studies [11, 28]. sidered in future trials, such as the children’s age,
However, this trial did not aim to examine the correl- their gender, the duration, the zinc format and the
ation between zinc deficiency and pneumonia, owing dosage.
to the lack of a healthy control group. The authors
hypothesize that the degree of pneumonia severity is CONCLUSION
associated with the level of zinc deficiency. To recapitulate, zinc supplementation, as an adjunct-
While this research followed random, blinded ive therapy, enhanced the outcomes of pneumonia
sampling and enrollment, the decision to discharge treatment by shortening the resolution period pneu-
the children from hospital was determined by the monia and the length of the hospital stay. It had a
attending physicians, which may have manipulated considerable effect on accelerating the time needed
426  Zinc Supplementation for Pneumonia

to normalize oxygen levels and body temperature; populations and options for its control. Food Nutr Bull
however, it had no impact on the remission of tach- 2004;25:S99–203.
ypnea and chest indrawing. Zinc was tolerated well 7. Bhutta ZA, Black RE, Brown KH, et al. Prevention of diar-
rhea and pneumonia by zinc supplementation in children
and the findings of the trial were not influenced by in developing countries: pooled analysis of randomized
the baseline zinc status. Henceforth, regardless of the controlled trials. Zinc Investigators’ Collaborative Group.
baseline zinc status, healthcare professionals should J Pediatr 1999;135:689–97.
consider zinc supplementation as a routine strategy 8. Valavi E, Hakimzadeh M, Shamsizadeh A, et al. The effi-
in the treatment protocol for children with cacy of zinc supplementation on outcome of children with
pneumonia. severe pneumonia. A randomized double-blind placebo-

Downloaded from https://academic.oup.com/tropej/article/66/4/419/5671781 by guest on 08 November 2024

controlled clinical trial. Indian J Pediatr 2011;78:1079–84.
9. Basnet S, Shrestha PS, Sharma A, et al. A randomized con-
ACKNOWLEDGEMENTS trolled trial of zinc as adjuvant therapy for severe pneumo-
We gratefully acknowledge the contribution of the children nia in young children. Pediatrics 2012;129:701–8.
and their families in this research. We also acknowledge the 10. Bose A, Coles CL, Gunavathi, et al. Efficacy of zinc in the
study physicians, nurses and all people who contributed to treatment of severe pneumonia in hospitalized children
this trial in different ways. <2 y old. Am J Clin Nutr 2006;83:1089–96; quiz 1207.
11. Sempertegui F, Estrella B, Rodriguez O, et al. Zinc as an
AUTHORS CONTRIBUTION adjunct to the treatment of severe pneumonia in
Both authors defined and developed the initial research idea. Ecuadorian children: a randomized controlled trial. Am J
They were also involved in the design and implementation of Clin Nutr 2014;99:497–505.
the study, as well as the analysis and interpretation of the 12. Shah GS, Dutta AK, Shah D, et al. Role of zinc in severe
results and the writing of the manuscript. Both authors have pneumonia: a randomized double bind placebo controlled
read and approved the final manuscript. study. Ital J Pediatr 2012;38:36.
13. World Health Organization. Revised WHO Classification
and Treatment of Pneumonia in Children at Health
FUNDING Facilities: Evidence Summaries. Geneva: WHO Press,
This study was supported by the Srinakharinwirot University, 2014.
Thailand [SWU 017/2561]. 14. Hotz C, Peerson JM, Brown KH. Suggested lower cutoffs
Conflict of interest: The authors declare that there is no of serum zinc concentrations for assessing zinc status: re-
conflict of interest. analysis of the second National Health and Nutrition
Examination Survey data (1976-1980). Am J Clin Nutr
2003;78:756–64.
REFERENCES 15. Qasemzadeh MJ, Fathi M, Tashvighi M, et al. The effect
1. Rudan I, O’Brien KL, Nair H, et al. Epidemiology and eti- of adjuvant zinc therapy on recovery from pneumonia in
ology of childhood pneumonia in 2010: estimates of inci- hospitalized children: a double-blind randomized con-
dence, severe morbidity, mortality, underlying risk factors trolled trial. Scientifica (Cairo) 2014;2014:694193.
and causative pathogens for 192 countries. J Glob Health 16. Shehzad N, Anwar MI, Muqaddas T. Zinc supplementa-
2013;3:010401. tion for the treatment of severe pneumonia in hospitalized
2. United Nations Children’s Fund (UNICEF). Ending children: a randomized controlled trial. Sudan J Paediatr
Child Deaths from Pneumonia and Diarrhea. New York, 2015;15:37–41.
USA: United Nations Children’s Fund, 2016. 17. Howie S, Bottomley C, Chimah O, et al. Zinc as an ad-
3. Le Saux N, Robinson J. Pneumonia in healthy Canadian junct therapy in the management of severe pneumonia
children and youth: practice points for management. among Gambian children: randomized controlled trial.
Paediatr Child Health 2011;16:417–24. J Glob Health 2018;8:010418.
4. Madhi SA, Levine OS, Hajjeh R, et al. Vaccines to prevent 18. Vinayak R, Behal M. Role of zinc as an adjuvant therapy in
pneumonia and improve child survival. Bull World Health severe pneumonia—a double blind placebo controlled
Organ 2008;86:365–72. randomized clinical trial. Panacea J Med Sci 2015;5:
5. Nguyen TK, Tran TH, Roberts CL, et al. Risk factors for 61–72.
child pneumonia—focus on the Western Pacific Region. 19. Yu Y, Lu L, Li SF, et al. Organic zinc absorption by the in-
Paediatr Respir Rev 2017;21:95–101. testine of broilers in vivo. Br J Nutr 2017;117:1086–94.
6. Brown KH, Rivera JA, Bhutta Z, et al. International Zinc 20. Gandia P, Bour D, Maurette JM, et al. A bioavailability
Nutrition Consultative Group (IZiNCG) technical docu- study comparing two oral formulations containing zinc
ment #1. Assessment of the risk of zinc deficiency in (Zn bis-glycinate vs. Zn gluconate) after a single
 Zinc Supplementation for Pneumonia  427

administration to twelve healthy female volunteers. Int J 25. Gammoh NZ, Rink L. Zinc in Infection and Inflammation.
Vitam Nutr Res 2007;77:243–8. Nutrients 2017;9:624.
21. Tie HT, Tan Q, Luo MZ, et al. Zinc as an adjunct to anti- 26. Jarosz M, Olbert M, Wyszogrodzka G, et al.
biotics for the treatment of severe pneumonia in children Antioxidant and anti-inflammatory effects of zinc. Zinc-
<5 years: a meta-analysis of randomised-controlled trials. dependent NF-jB signaling. Inflammopharmacology
Br J Nutr 2016;115:807–16. 2017;25:11–24.
22. Wang L, Song Y. Efficacy of zinc given as an adjunct to the 27. Arica S, Arica V, Dag H, et al. Serum zinc levels in
treatment of severe pneumonia: a meta-analysis of children of 0-24 months diagnosed with
randomized, double-blind and placebo-controlled trials. pneumonia admitted to our clinic. Int J Clin Exp Med
Clin Respir J 2018;12:857–64. 2011;4:227–33.

Downloaded from https://academic.oup.com/tropej/article/66/4/419/5671781 by guest on 08 November 2024

23. Hennig B, Wang Y, Ramasamy S, et al. Zinc deficiency 28. Wadhwa N, Chandran A, Aneja S, et al. Efficacy of zinc
alters barrier function of cultured porcine endothelial cells. given as an adjunct in the treatment of severe and very se-
J Nutr 1992;122:1242–7. vere pneumonia in hospitalized children 2-24 mo of age: a
24. Sazawal S, Black RE, Jalla S, et al. Zinc supplementation randomized, double-blind, placebo-controlled trial. Am J
reduces the incidence of acute lower respiratory infections Clin Nutr 2013;97:1387–94.
in infants and preschool children: a double-blind, con- 29. Lonnerdal B. Dietary factors influencing zinc absorption.
trolled trial. Pediatrics 1998;102:1–5. J Nutr 2000;130:1378s–83s.