Efficacy of Oral Zinc Supplementation in Radiologically Confirmed Pneumonia: Secondary Analysis of a Randomized Controlled Trial

Bagri, Narendra Kumar; Bagri, Neha; Jana, Manisha; Gupta, Arun Kumar; Wadhwa, Nitya; Lodha, Rakesh; Kabra, Sushil Kumar; Chandran, Aruna; Aneja, Satinder; Chaturvedi, Mona K.; Sodhi, Jitender; Fitzwater, Sean; Chandra, Jagdish; Rath, Bimbadhar; Kainth, Udaypal S; Saini, Sharanjot; Black, Robert E.; Santosham, Mathuram; Bhatnagar, Shinjini

doi:10.1093/tropej/fmx036

Cited by 6 publications

(19 citation statements)

References 18 publications

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“…Zinc supplementation was shown to reduce the respiratory morbidity of ALRI in children less than 5 years of age who were zinc deficient (8). Studies examining the clinical effects of zinc for treating pneumonia in children have shown conflicting results, with some studies showing a beneficial effect on the duration of recovery and severity but with other studies suggesting that zinc has no treatment benefit (9)(10)(11)(12)(13). Although the necessary role of zinc as a micronutrient in various physiological functions has been demonstrated, the molecular mechanism underlying the effects of zinc during viral infections has not been elucidated.…”

mentioning

confidence: 99%

Respiratory Syncytial Virus-Induced Oxidative Stress Leads to an Increase in Labile Zinc Pools in Lung Epithelial Cells

Khan

Singla

Samal

et al. 2020

mSphere

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Zinc supplementation in cell culture has been shown to inhibit various viruses, like herpes simplex virus, rotavirus, severe acute respiratory syndrome (SARS) coronavirus, rhinovirus, and respiratory syncytial virus (RSV). However, whether zinc plays a direct antiviral role in viral infections and whether viruses have adopted strategies to modulate zinc homeostasis have not been investigated. Results from clinical trials of zinc supplementation in infections indicate that zinc supplementation may be beneficial in a pathogen- or disease-specific manner, further underscoring the importance of understanding the interaction between zinc homeostasis and virus infections at the molecular level. We investigated the effect of RSV infection on zinc homeostasis and show that RSV infection in lung epithelial cells leads to modulation of zinc homeostasis. The intracellular labile zinc pool increases upon RSV infection in a multiplicity of infection (MOI)-dependent fashion. Small interfering RNA (siRNA)-mediated knockdown of the ubiquitous zinc uptake transporter ZIP1 suggests that labile zinc levels are increased due to the increased uptake by RSV-infected cells as an antiviral response. Adding zinc to culture medium after RSV infection led to significant inhibition of RSV titers, whereas depletion of zinc by a zinc chelator, N,N,N′,N′-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) led to an increase in RSV titers. The inhibitory effect of zinc was specific, as other divalent cations had no effect on RSV titers. Both RSV infection and zinc chelation by TPEN led to reactive oxygen species (ROS) induction, whereas addition of zinc blocked ROS induction. These results suggest a molecular link between RSV infection, zinc homeostasis, and oxidative-stress pathways and provide new insights for developing strategies to counter RSV infection. IMPORTANCE Zinc deficiency rates in developing countries range from 20 to 30%, and zinc supplementation trials have been shown to correct clinical manifestations attributed to zinc deficiency, but the outcomes in the case of respiratory infections have been inconsistent. We aimed at understanding the role of zinc homeostasis in respiratory syncytial virus (RSV) infection. Infection of lung epithelial cell lines or primary small-airway epithelial cells led to an increase in labile zinc pools, which was due to increased uptake of zinc. Zinc supplementation inhibited RSV replication, whereas zinc chelation had an opposing effect, leading to increases in RSV titers. Increases in labile zinc in RSV-infected cells coincided with induction of reactive oxygen species (ROS). Both zinc depletion and addition of exogenous ROS led to enhanced RSV infection, whereas addition of the antioxidant inhibited RSV, suggesting that zinc is part of an interplay between RSV-induced oxidative stress and the host response to maintain redox balance.

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confidence: 99%

Respiratory Syncytial Virus-Induced Oxidative Stress Leads to an Increase in Labile Zinc Pools in Lung Epithelial Cells

Khan

Singla

Samal

et al. 2020

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“…After literature screening, 50 articles published between 1996 and 2022 were retained for the systematic review. The studies were conducted in the following continents: 33 in Asia, 22,26,27,29,[31][32][33][35][36][37][38][39][40][41]43,45,[47][48][49][50][51][52][53][54][57][58][59][60][61][62][65][66][67] eight in Africa, 23,25,34,42,44,55,63,68 five in South America, 20,21,24,28,46 two in North America, 56,64 one in Central America, 19 and one in Oceania. 30 Four trials were conducted ...…”

Section: Systematic Reviewmentioning

confidence: 99%

A systematic review and meta‐analysis on nutritional and dietary interventions for the treatment of acute respiratory infection in pediatric patients: An EAACI taskforce

Milani,

Alberti,

Abodi

et al. 2024

Allergy

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Acute respiratory infections are a major cause of morbidity and mortality in children worldwide. Dietary and nutritional interventions, including minerals and vitamin supplementation, have been explored as potential treatments for these infections. However, the evidence on their efficacy is limited and inconclusive. This systematic review and meta‐analysis aim to provide a comprehensive summary of the available evidence on the effectiveness of dietary and nutritional interventions for treating acute respiratory tract infections in children. A systematic review was conducted according to the PRISMA 2020 guidelines in April 2022 and updated in April 2023. Clinical trials focusing on dietary or nutritional interventions, including supplementations, in children with acute respiratory tract infections were included. The selection of interventions and outcomes was based on biological plausibility. Data were extracted using a standardized form, and the risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta‐analysis was performed using random‐effect models. A total of 50 studies were included in the review. Four trials were conducted in low, 32 in lower‐middle, 12 in upper‐middle, and only two in high‐income countries. The studies evaluated various dietary interventions, including zinc, vitamin A, vitamin E, vitamin D, and probiotics. The results of individual studies on the efficacy of these interventions were mixed, with some showing positive effects on clinical outcomes such as duration of symptoms, while others showed no significant impact. Meta‐analysis was conducted for zinc supplementation in children with pneumonia, and the pooled results suggested a potential limited benefit in terms of reduced hospital length of stay but not time to recovery. Meta‐analyses on vitamin D did not show any effect in children with pneumonia. This systematic review fills a critical gap in the literature by synthesizing the available evidence on the efficacy and safety of nutritional or dietary interventions for acute respiratory tract infections in children. The findings indicate no dietary or nutritional intervention can currently be recommended for the routine treatment of respiratory tract infections in children based on single supplement studies. The metanalysis suggests that zinc supplementation might have a beneficial effect on length of hospitalization in children with pneumonia. New studies are needed to establish more conclusive evidence for pediatric acute respiratory diseases especially for children living in a context of high‐income countries.

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“…Dari tiga belas studi, tujuh studi tidak memiliki data yang lengkap; tidak melaporkan kadar zink awal, [12][13][14][15][16][17] dan tidak melaporkan luaran yang diteliti. 18 Satu studi memberikan intervensi tambahan selain zink dan antibiotik standar untuk pneumonia, 19 serta satu studi setelah dilakukan telaah kritis dinilai kurang baik. 20 Dengan demikian terdapat empat artikel yang akan digunakan sebagai acuan dalam penyusunan systematic review ini.…”

Section: Hasil 31 Seleksi Studiunclassified

Efektivitas Suplementasi Zink Terhadap Lama Rawat Inap pada Pasien Pneumonia Anak: A Systematic Review of Randomized Controlled Trials

Dewi,

Mayangsari,

Adnyana

2023

eum

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Zinc supplementation was reported increasing pneumonia in child outcomes, which one is the length of hospital stay, but still controversial. This review will discuss about effectivity of zinc supplementation for the length of hospital stay in children hospitalized with pneumonia in forms systematic review. Searching was performed at CENTRAL, PubMed, and ProQuest for journal published from 2015 to 2020 which evaluate the effectivity of zinc supplementation for the length of hospital stay in children hospitalized with pneumonia. This review based on writing guidelines by Cochrane Textbook of Systematic Review. There are four studies relevant to this review. All studies are blinded study. A total of 1.359 children hospitalized with pneumonia, percentage of a male around 59%. A total of 680 participants received zinc supplementation as addition for standard antibiotics. Participants were 1 to 60 months of age. All studies measure baseline serum zinc levels. Two studies reported significant results, while two other study conversely. Effectivity of zinc supplementation has not been concluded yet. Based on critical appraisal, the author attends to agree with two studies that conduct in Asia, in which the populations were similar to Indonesia. In that study found zinc supplementation effective to decreases the length of hospital stay in children hospitalized with pneumonia. There is no fatal adverse effect of zinc supplementation was reported.

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Efficacy of Oral Zinc Supplementation in Radiologically Confirmed Pneumonia: Secondary Analysis of a Randomized Controlled Trial

Abstract: There was no significant beneficial effect of zinc on the duration of recovery or risk of treatment failure in children with radiologically confirmed pneumonia.

Cited by 6 publications

References 18 publications

Respiratory Syncytial Virus-Induced Oxidative Stress Leads to an Increase in Labile Zinc Pools in Lung Epithelial Cells

Respiratory Syncytial Virus-Induced Oxidative Stress Leads to an Increase in Labile Zinc Pools in Lung Epithelial Cells

A systematic review and meta‐analysis on nutritional and dietary interventions for the treatment of acute respiratory infection in pediatric patients: An EAACI taskforce

Efektivitas Suplementasi Zink Terhadap Lama Rawat Inap pada Pasien Pneumonia Anak: A Systematic Review of Randomized Controlled Trials

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