Differential Effects of Zinc in Severe Pneumonia in Children

Abstract

We read with great interest the article by Bansal et al. [1]. The authors had conducted a clinical trial and found that, zinc supplementation did not reduce recovery time and duration of hospital stay in children with severe acute lower respiratory tract infection (ALRTI). The study is well described, but there are few points that need comment. The authors describe that; zincmay bemore effective in the treatment of serious bacterial pneumonias, and not in viral pneumonias or bronchiolitis, which are predominantly viral illnesses. In their study, the percentage of children with wheezing was quite high (68.5%), and though they analyzed the outcome measures for wheezy and non-wheezy children separately, they did not find any significant difference in outcome. Actually, there is no published study examining the role of zinc in severe bacterial versus viral pneumonia. So, these are all speculations that zinc does not help children with pneumonia due to viral etiology (based on proportion of children with wheezing). If we look at the mechanism, how zinc might be beneficial in pneumonia, the following points need mention. Zinc deficiency enhances airway inflammation and cellular damage, whereas zinc supplementation might protect the lung from inflammatory states. Mechanisms for anti-inflammatory action of zinc in the respiratory tract include: blocking the binding of leucocytes to the endothelial cells via interaction between intercellular adhesion molecule (ICAM) -1 and leucocyte associated antigen-1 [2], inhibiting the release of preformed mediators from inflammatory cells, etc. So, the beneficial effects of zinc in severe pneumonia might depend upon the extent of inflammation and its resolution rate, as well as on the acute phase response mediated by the cytokines. Zinc also has potent antiviral action that includes: prevents the formation of viral capsid proteins (inhibiting in vitro replication of viruses) [3], prevents the virus from combining with the ICAM-1 (inhibiting viral entry into the cell), may induce the production of interferon (having non-specific antiviral actions) [4], inhibit human prostaglandin metabolism (thus decreasing inflammation). So, there is no reason for the differential effects of zinc in severe pneumonia according to the etiology. If this is proved, zinc may find its place in management of severe pneumonia as in acute diarrhea. We hope that, future trials should focus on this issue and try to compare the differential effects of zinc in severe bacterial and viral pneumonia. This might be difficult, but some suggestions include: use of chest radiograph in addition to clinical definition of pneumonia, designing the studies in a way to detect the difference in the subgroup of children without wheezing or totally excluding wheezing children, microbiological criteria (culture, PCR, antigen and/or antibody detection, etc), use of inflammatory markers (C reactive protein, procalcitonin), etc.