Immunomodulation by Zinc Supplementation in Children With Pneumonia
Condition: Pneumonia; Children, Only
MeSH terms: Pneumonia
Study type: Interventional
Phase: Phase 1

Summary: 
      Pneumonia is one of the main causes of morbidity and mortality in the world, especially in
      developing countries like ours.

      The National Health and Nutrition Survey of Mexico, in 2006 showed underweight in 472,890
      (5%) children under five years, low height in 1,194,805 (12.7%) and wasting in153,000 (1.6%)
      children. Zinc is decreased in malnutrition and is an essential cofactor for many proteins
      involved in cellular processes. Zinc deficiency leads to a decrease in the number of T cells,
      the ratio of Th1 to Th2 cells and the production of Th1 cytokines such as interferon gamma,
      with alteration in T cell mediated immunity. In malnourished children zinc supplementation
      restores the immune response. Reports of zinc supplementation in children with pneumonia are
      controversial.

      The aims of this study are to evaluate the immunomodulatory effect of zinc supplementation in
      the clinical course of children with pneumonia, to evaluate the lymphoproliferative and
      cytokine response in these children and to explore whether the viral or bacterial etiology is
      related to the clinical response to supplementation with this micronutrient.

      A clinical, randomized, prospective, controlled, double blinded study will be carried out.
      Children from 1 month to 5 years of age will be included, with the clinical and / or
      radiological diagnosis of pneumonia that enter the emergency room of the participant
      institutions. Empirical treatment for pneumonia will begin and each patient will be
      randomized 1:1 in 2 groups. One will receive zinc supplementation and another a placebo
      (glucose). Samples will be taken to determine the etiology (nasal lavage for multiplex
      polymerase chain reaction for 16 respiratory viruses and 6 bacteria) and a blood sample to
      measure the cytokine pattern and the lymphoproliferative response. After 7 days of treatment,
      a second sample will be taken for immunological studies (cytokine pattern and
      lymphoproliferative response). The following parameters will be measured to evaluate the
      clinical evolution: respiratory rate, temperature, oxygen saturation, inability to eat,
      duration of cough, rales, temperature normalization time, normalization time of oxygen
      saturation, normalization time of the respiratory rate, hospitalization time and outcome
      (discharge due to clinical improvement or death). A correlation will be made between the
      improvement in clinical parameters and mortality in the zinc supplementation group and the
      probable bacterial or viral etiology.
    

Detailed description: 
      Background: Pneumonia is one of the main causes of morbidity and mortality in the world,
      especially in developing countries like ours. Of an estimated 8.795 million deaths in
      children under 5 in the world in 2008, 68% were infectious causes, with the highest
      percentage due to pneumonia in 18%, followed by diarrhea in 15% and malaria in 8%, 41% of the
      deaths were in neonates, pneumonia being the 4th cause of death in this age group. Acute
      respiratory infections, diarrhea and malnutrition together cause 10% of deaths among children
      under 1 year of age. In Mexico, a pneumonia mortality rate of 120 per 100,000 inhabitants is
      reported in children under 1 year of age, and 5 deaths per 100,000 inhabitants in children
      from 1 to 4 years of age in 2007.

      The results of the National Health and Nutrition Survey (ENSANUT), carried out in 2006 by the
      National Institute of Public Health, showed that 472,890 children under five years of age
      were classified as underweight (5%), 1,194,805 with low height (12.7%) and around 153,000
      children with wasting (1.6%). The overall prevalence of anemia in urban areas was 22.8%,
      while in rural areas was 26.1%. Likewise, it is known that there are specific deficiencies of
      some micronutrients, such as vitamin A, C, E, zinc, iron, folic acid and iodine, among
      others. Malnourished children loose between 12 and 15% of their intellectual potential, have
      a higher risk of infectious diseases 8 to 12 times more than a healthy child and are more
      prone to chronic degenerative diseases. Malnutrition causes among others an effect of
      immunosuppression. One of the micronutrients that is decreased in malnutrition is zinc. Zinc
      is an essential cofactor for many proteins involved in cellular processes such as
      differentiation, proliferation and apoptosis. During zinc deficiency, the development of T
      lymphocytes, the polarization in effector cells and their function are altered. This leads to
      a decrease in the number of T cells, a decrease in the ratio of Th1 to Th2 cells with a
      decrease in the production of Th1 cytokines such as interferon gamma, and alteration in the
      defense mediated by T cells. In malnourished children zinc supplementation restores the
      immune response. Reports of zinc supplementation in children with infectious diseases are
      controversial. A study in Uganda reports that supplementation with zinc in children from 6
      months to 5 years of age with severe pneumonia decreased the mortality from 12% to 4%, with a
      relative risk reduction of 0.67. Cellular immunity plays a very important role in the defense
      of the host against viruses and bacteria, zinc supplementation in children who have some
      degree of malnutrition and who suffer a serious infection could improve the immune response
      and improve the ability to respond to acute infection.

      The aim of this study is to evaluate the immunomodulatory effect of zinc supplementation in
      the clinical course of children with pneumonia, to evaluate the lymphoproliferative and
      cytokine response in these children and to explore whether the viral or bacterial etiology is
      related to the clinical response to supplementation with this micronutrient.

      Methods: This is a clinical, randomized, prospective, controlled, double blinded study.
      Children from 1 month to 5 years of age will be included, with the clinical and / or
      radiological diagnosis of pneumonia that enter the emergency room of the participant
      institutions. Empirical treatment for pneumonia will begin and each patient will be
      randomized 1:1 in 2 groups. One will receive zinc supplementation (10 mg of zinc sulfate in
      children younger than 1 year old and 20 mg of zinc sulfate in children older than 1 year old)
      and another a placebo (glucose 10 mg). Samples will be taken to determine the etiology
      (pharyngeal exudate, nasal lavage for multiplex polymerase chain reaction for 16 respiratory
      viruses and 6 bacteria) and a blood sample to measure the cytokine pattern and the
      lymphoproliferative response. After 7 days of treatment, a second sample will be taken for
      immunological studies (cytokine pattern and lymphoproliferative response). The following
      parameters will be measured to evaluate the clinical evolution: respiratory rate,
      temperature, oxygen saturation, inability to eat, duration of cough, crackling, temperature
      normalization time, normalization time of oxygen saturation, normalization time of the
      respiratory rate, hospitalization time and outcome (discharge due to clinical improvement or
      death). A correlation will be made between the improvement in clinical parameters and
      mortality in the zinc supplementation group and the probable bacterial or viral etiology.
    

Intervention name(s): Zinc sulfate; Glucose
Intervention type(s): Drug; Other
Intervention description(s): Zinc sulfate 10 mg for children younger than 1 year old, 20 mg for children older than 1 year old, will be diluted in 1 ml of sterile water and administered orally every day in the morning during hospitalization; The placebo group will receive glucose diluted in 1 ml of sterile water orally every day during hospitalization
Other intervention name(s): Zinc
Intervention MeSH terms: Zinc; Zinc Sulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Pneumonia; Zinc supplementation; Cytokines; Lymphoproliferation; Viruses; Respiratory bacteria