Zinc in Acute Bronchiolitis: Is It Really Ineffective?

Dear Editor

I read with great interest the article by Heydarian et al [1]. The authors had conducted a clinical trial and found that zinc supplementation did not benefit clinical manifestations of acute bronchiolitis. The study is well described, but there are few points that need comment.

The authors described that bottles of drug and placebo were similar in size and shape. However, it is well known that, the most important factor in zinc trials have been problem in blinding due to bad taste of zinc salts. There is also no description of the adverse events in the study (even in the zinc group), which is really surprising[2]. So, author's description of double-blinding might have been compromised, with resultant affection of the findings of the study. The authors also excluded children with pneumonia. But, how did they exclude children with viral pneumonia (as both are difficult to distinguish clinically and radiologically)? This is an important question, as it has been found that zinc might not be effective in viral pneumonia[3]. It is also not clear, whether the person responsible for the administration of the intervention and evaluation of clinical signs of bronchiolitis is same or different. Because, if both have been done by the same person, then it might have also affected blinding and resultant data collection. These factors question the validity of the result.

The authors also described that, as studies using zinc have found conflicting results in pneumonia, they conducted this trial to find if zinc benefits another acute lower respiratory tract infection (ALRTI), namely acute bronchiolitis. But they also did not find any beneficial effect. This can be explained as follows. It is known that, benefit from zinc administration seems to increase after 100 hours of illness, and might be inherent in the mechanism of the zinc effect [4]. So, in an acute illness such as ALRTI, there probably is insufficient time for mounting an immune response to favorably modify the acute illness besides favorably modifying the acute phase response. Secondly, early in an infection zinc is also shifted into the liver due to the acute phase response, whereby it is sequestered for purposes of removing it from pathogen access as well as for reviving up the immune response[5]. This adds weight to the assessment that zinc may work by different mechanisms in ALRTI and acute diarrhea.

Though the authors do not have any explanation why respiratory distress symptoms were improved significantly 24 hours after therapy in the control group, the same has not been shown in the Table 2 (I could not find any result to be significant between the two groups in the table, even after 48 or 72 hrs).

Lastly, the authors describe that, zinc administration does not improve clinical manifestations and hospitalization, in subjects with normal serum zinc level before treatment. However, this is not true if we consider the following points. First, plasma zinc levels are not the most reliable indicators of zinc status in the body[6]. In children with acute infection, zinc level decreases as part of an acute phase response and increases during recovery[6]. Second, plasma zinc level rises even in non zinc supplemented children when they recover from ALRTI, a finding supported by the increase in plasma zinc at discharge among children who did not receive zinc in many of the zinc-pneumonia trials [3, 7, 8].

To conclude, more research is needed in this area before any firm conclusion can be made. For the result to be meaningful, above factors must be taken care of.

Conflict of Interest

None