Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial. Zinc supplementation in severe acute lower respiratory tract infection in children: a triple-blind randomized placebo controlled trial. A randomized controlled trial of the effect of zinc as adjuvant therapy in children 2-35 mo of age with severe or nonsevere pneumonia in Bhaktapur, Nepal.
Pneumonia is a leading cause of morbidity and mortality in young children. Early reversal of severity signs--chest indrawing, hypoxia, and tachypnoea--improves outcome. We postulated that zinc, an acute phase reactant, would shorten duration of severe pneumonia and time in hospital.
                In a double-blind placebo-controlled clinical trial in Matlab Hospital, Bangladesh, 270 children aged 2-23 months were randomised to receive elemental zinc (20 mg per day) or placebo, plus the hospital's standard antimicrobial management, until discharge. The outcomes were time to cessation of severe pneumonia (no chest indrawing, respiratory rate 50 per min or less, oxygen saturation at least 95% on room air) and discharge from hospital. Discharge was allowed when respiratory rate was 40 per minute or less for 24 consecutive hours while patients were maintained only on oral antibiotics.
                The group receiving zinc had reduced duration of severe pneumonia (relative hazard [RH]=0.70, 95% CI 0.51-0.98), including duration of chest indrawing (0.80, 0.61-1.05), respiratory rate more than 50 per min (0.74, 0.57-0.98), and hypoxia (0.79, 0.61-1.04), and overall hospital duration (0.75, 0.57-0.99). The mean reduction is equivalent to 1 hospital day for both severe pneumonia and time in hospital. All effects were greater when children with wheezing were omitted from the analysis.
                Adjuvant treatment with 20 mg zinc per day accelerates recovery from severe pneumonia in children, and could help reduce antimicrobial resistance by decreasing multiple antibiotic exposures, and lessen complications and deaths where second line drugs are unavailable. To evaluate the efficacy of zinc supplementation on duration of illness in children with severe acute lower respiratory tract infection (ALRTI).
                This randomized triple-blind placebo-controlled trial was conducted in pediatric emergency of a teaching referral hospital. Children in the age group of 2-24 months presenting to pediatric emergency with severe ALRTI were included. Eligible children were randomly allocated to zinc (n=53) or control (n=53) groups. Zinc group received 20 mg of elemental zinc per day (5 ml syrup per day) as a single daily dose for 5 days. Control group received an equal amount of placebo which was appropriately modified to give the taste, smell, color and consistency similar to zinc mixture. Primary outcome was 'time to be asymptomatic', a composite outcome defined as resolution of all four of the following: danger signs, respiratory distress, tachypnea and hypoxia in room air.
                Age, gender, nutritional status, pretreatment zinc levels and other demographic and clinical variables were similar in the two groups. 'Time to be asymptomatic' was comparable in the two groups (h; median (IQR): 60 (24-78) vs. 54 (30-72), P=0.98]. At any time point a similar proportion of children were symptomatic in both the groups. Time to resolution of respiratory distress, tachypnea, dangers signs and hypoxia were also similar in two groups. Duration of hospital stay was shorter by 9 h in the zinc group but the difference was statistically insignificant.
                Zinc supplementation did not reduce recovery time and duration of hospital stay in children with ALRTI. Larger randomized controlled trials are needed to evaluate role of zinc in ALRTI. Pneumonia is a leading cause of illness and death in young children. Interventions to improve case management of pneumonia are needed.
                Our objective was to measure the effect of zinc supplementation in children with pneumonia in a population in which zinc deficiency is common.
                In a double-blind, placebo-controlled clinical trial, children aged 2-35 mo with severe (n = 149) or nonsevere (n = 2479) pneumonia defined according to criteria established by the World Health Organization were randomly assigned to receive zinc (10 mg for children aged 2-11 mo, 20 mg for children aged > or =12 mo) or placebo daily for 14 d as an adjuvant to antibiotics. The primary outcomes were treatment failure, defined as a need for change in antibiotics or hospitalization, and time to recovery from pneumonia.
                One of 5 children did not respond adequately to antibiotic treatment; the odds ratios between zinc and placebo groups for treatment failure were 0.95 (95% CI: 0.78, 1.2) for nonsevere pneumonia and 0.97 (95% CI: 0.42, 2.2) for severe pneumonia. There was no difference in time to recovery between zinc and placebo groups for nonsevere (median: 2 d; hazard ratio: 1.0; 95% CI: 0.96, 1.1) or severe (median: 4 d; hazard ratio: 1.1; 95% CI: 0.79, 1.5) pneumonia. Regurgitation or vomiting < or =15 min after supplementation was observed more frequently among children in the zinc group than among those in the placebo group during the supplementation period (37% compared with 13%; odds ratio: 0.25; 95% CI: 0.20, 0.30).
                Adjuvant treatment with zinc neither reduced the risk of treatment failure nor accelerated recovery in episodes of nonsevere or severe pneumonia. This trial was registered at clinicaltrials.gov as NCT00148733.
Evidence provided in this review is insufficient to recommend the use of zinc as an adjunct to standard antibiotic therapy for pneumonia in children aged two to 35 months.