Efficacy of zinc given as an adjunct to the treatment of severe pneumonia: A meta‐analysis of randomized, double‐blind and placebo‐controlled trials
Linlin Wang, Yuanlin Song
The Clinical Respiratory Journal, doi:10.1111/crj.12646
Background: Pneumonia is a major cause of morbidity and mortality of children. Zinc is known to play a central role in the immune system. The deficiency of zinc increased susceptibility to infectious diseases. Objective: To investigate the clinical efficacy of zinc given as an adjunct therapy to the treatment of severe pneumonia.
Methods: The PubMed, Embase, MEDLINE TM and the Cochrane Central Register of Controlled Trials were searched to identify all randomized, double-blind and placebo-controlled (DBPC) trials which evaluated the clinical efficacy of zinc given as an adjunct in the treatment of severe pneumonia and published between January 1966 and October 2015. Results: Six randomized DBPC trials including 2216 patients with severe pneumonia were eligible. The results suggested that zinc given as an adjunct therapy to the treatment of severe pneumonia had no significant improvement of treatment failure (RR 5 0.97, P 5 .71) and change of antibiotic therapy (RR 5 1.09, P 5 .52). We also found a favorable trend for clinical deterioration of severe pneumonia but with no statistical significance (RR 5 0.88, P 5 .55). Zinc produced a significant reduction in mortality caused by severe pneumonia (RR 5 0.43, P 5 .01). Conclusions: Zinc given as an adjunct to the treatment of severe pneumonia is effective in reducing the mortality of severe pneumonia, and has no significant effects on treatment failure and change of antibiotic therapy.
CONFLICT OF INTEREST The authors had no conflicts of interest to declare in relation to this article.
AUTHOR CONTRIBUTIONS Searched the database, judged study eligibility, extracted data and did the meta-analysis and drafted the article: Wang Designed the study and revised this paper: Song All authors have read and approve this version of the article.
References
Bao, Knoell, Zinc modulates airway epithelium susceptibility to death receptor-mediated apoptosis, Am J Physiol Lung Cell Mol Physiol
Bao, Prasad, Beck, Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients, Transl Res
Basnet, Shrestha, Sharma, A randomized controlled trial of zinc as adjuvant therapy for severe pneumonia in young children, Pediatrics
Bhutta, Black, Brown, Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group, J Pediatr
Castillo-Duran, Heresi, Fisberg, Uauy, Controlled trial of zinc supplementation during recovery from malnutrition: effects on growth and immune function, Am J Clin Nutr
Fu, Ding, Zhuang, Zhou, Effects of zinc supplementation on the incidence of mortality in preschool children: a meta-analysis of randomized controlled trials, PLoS One
Higgins, Altman, Sterne, Chapter 8: assessing risk of bias in included studies
Lazzerini, Ronfani, Oral zinc for treating diarrhoea in children, Cochrane Database Syst Rev
Liu, Johnson, Cousens, Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000, Lancet
Raqib, Roy, Rahman, Effect of zinc supplementation on immune and inflammatory responses in pediatric patients with shigellosis, Am J Clin Nutr
Roth, Richard, Black, Zinc supplementation for the prevention of acute lower respiratory infection in children in developing countries: meta-analysis and meta-regression of randomized trials, Int J Epidemiol
Semp Ertegui, Estrella, Rodríguez, Zinc as an adjunct to the treatment of severe pneumonia in Ecuadorian children: a randomized controlled trial, Am J Clin Nutr
Shah, Dutta, Shah, Mishra, Role of zinc in severe pneumonia: a randomized double bind placebo controlled study, Ital J Pediatr
Shankar, Prasad, Zinc and immune function: the biological basis of altered resistance to infection, Am J Clin Nutr
Srinivasan, Ndeezi, Mboijana, Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial, BMC Med
Valentiner-Branth, Shrestha, Chandyo, 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, Am J Clin Nutr
Wadhwa, Chandran, Aneja, Efficacy of zinc given as an adjunct in the treatment of severe and very severe pneumonia in hospitalized children 2-24 mo of age: a randomized, double-blind, placebo-controlled trial, Am J Clin Nutr
Walker, Ezzati, Black, Global and regional child mortality and burden of disease attributable to zinc deficiency, Eur J Clin Nutr
Yakoob, Theodoratou, Jabeen, Preventive zinc supplementation in developing countries: impact on mortality and morbidity due to diarrhea, pneumonia and malaria, BMC Public Health
{ 'indexed': {'date-parts': [[2023, 3, 22]], 'date-time': '2023-03-22T18:54:48Z', 'timestamp': 1679511288408},
'reference-count': 19,
'publisher': 'Wiley',
'issue': '3',
'license': [ { 'start': { 'date-parts': [[2017, 5, 31]],
'date-time': '2017-05-31T00:00:00Z',
'timestamp': 1496188800000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'http://doi.wiley.com/10.1002/tdm_license_1.1'},
{ 'start': { 'date-parts': [[2017, 5, 31]],
'date-time': '2017-05-31T00:00:00Z',
'timestamp': 1496188800000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'http://onlinelibrary.wiley.com/termsAndConditions#vor'}],
'funder': [ { 'DOI': '10.13039/501100001809',
'name': 'National Natural Science Foundation of China',
'doi-asserted-by': 'publisher',
'award': ['81100046, 30930090, and 81170056']},
{ 'DOI': '10.13039/501100012150',
'name': 'Shanghai Leading Academic Discipline Project',
'doi-asserted-by': 'crossref',
'award': ['B115']},
{ 'name': 'Shanghai Institutions of Higher Learning and Key Medical grant from Shanghai '
'Science and Technology Committee',
'award': ['11411951102 and 12JC1402300']},
{'name': 'State Key Basic Research Program (973) project', 'award': ['2015CB553404']},
{'name': 'Doctoral Fund of Ministry of Education of China', 'award': ['20130071110044']}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'published-print': {'date-parts': [[2018, 3]]},
'DOI': '10.1111/crj.12646',
'type': 'journal-article',
'created': {'date-parts': [[2017, 5, 10]], 'date-time': '2017-05-10T00:02:42Z', 'timestamp': 1494374562000},
'page': '857-864',
'source': 'Crossref',
'is-referenced-by-count': 40,
'title': 'Efficacy of zinc given as an adjunct to the treatment of severe pneumonia: A meta-analysis of '
'randomized, double-blind and placebo-controlled trials',
'prefix': '10.1111',
'volume': '12',
'author': [ { 'ORCID': 'http://orcid.org/0000-0001-9332-284X',
'authenticated-orcid': False,
'given': 'Linlin',
'family': 'Wang',
'sequence': 'first',
'affiliation': [ { 'name': 'Department of Pulmonary Medicine; Shanghai Respiratory Research '
'Institute, Zhongshan Hospital, Fudan University; Shanghai 200032 '
'China'}]},
{ 'given': 'Yuanlin',
'family': 'Song',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Pulmonary Medicine; Shanghai Respiratory Research '
'Institute, Zhongshan Hospital, Fudan University; Shanghai 200032 '
'China'},
{'name': 'Shanghai Public Health Clinical Center; Shanghai 201508 China'},
{ 'name': 'Zhongshan Hospital, Qingpu Branch, Fudan University; Shanghai '
'201700 China'}]}],
'member': '311',
'published-online': {'date-parts': [[2017, 5, 31]]},
'reference': [ { 'issue': '9832',
'key': '10.1111/crj.12646-BIB0001|crj12646-cit-0002',
'doi-asserted-by': 'crossref',
'first-page': '2151',
'DOI': '10.1016/S0140-6736(12)60560-1',
'article-title': 'Global, regional, and national causes of child mortality: an updated '
'systematic analysis for 2010 with time trends since 2000',
'volume': '379',
'author': 'Liu',
'year': '2012',
'journal-title': 'Lancet.'},
{ 'issue': '2 suppl',
'key': '10.1111/crj.12646-BIB0002|crj12646-cit-0003',
'doi-asserted-by': 'crossref',
'first-page': '447S',
'DOI': '10.1093/ajcn/68.2.447S',
'article-title': 'Zinc and immune function: the biological basis of altered resistance to '
'infection',
'volume': '68',
'author': 'Shankar',
'year': '1998',
'journal-title': 'Am J Clin Nutr.'},
{ 'key': '10.1111/crj.12646-BIB0003|crj12646-cit-0004',
'first-page': 'CD005436',
'article-title': 'Oral zinc for treating diarrhoea in children',
'volume': '3',
'author': 'Lazzerini',
'year': '2008',
'journal-title': 'Cochrane Database Syst Rev.'},
{ 'issue': 'suppl 3',
'key': '10.1111/crj.12646-BIB0004|crj12646-cit-0005',
'doi-asserted-by': 'crossref',
'first-page': 'S23',
'DOI': '10.1186/1471-2458-11-S3-S23',
'article-title': 'Preventive zinc supplementation in developing countries: impact on '
'mortality and morbidity due to diarrhea, pneumonia and malaria',
'volume': '11',
'author': 'Yakoob',
'year': '2011',
'journal-title': 'BMC Public Health.'},
{ 'issue': '6',
'key': '10.1111/crj.12646-BIB0005|crj12646-cit-0006',
'doi-asserted-by': 'crossref',
'first-page': '689',
'DOI': '10.1016/S0022-3476(99)70086-7',
'article-title': 'Prevention of diarrhea and pneumonia by zinc supplementation in '
'children in developing countries: pooled analysis of randomized '
'controlled trials. Zinc Investigators’ Collaborative Group',
'volume': '135',
'author': 'Bhutta',
'year': '1999',
'journal-title': 'J Pediatr.'},
{ 'issue': '3',
'key': '10.1111/crj.12646-BIB0006|crj12646-cit-0007',
'doi-asserted-by': 'crossref',
'first-page': '795',
'DOI': '10.1093/ije/dyp391',
'article-title': 'Zinc supplementation for the prevention of acute lower respiratory '
'infection in children in developing countries: meta-analysis and '
'meta-regression of randomized trials',
'volume': '39',
'author': 'Roth',
'year': '2010',
'journal-title': 'Int J Epidemiol.'},
{ 'issue': '3',
'key': '10.1111/crj.12646-BIB0007|crj12646-cit-0008',
'doi-asserted-by': 'crossref',
'first-page': '497',
'DOI': '10.3945/ajcn.113.067892',
'article-title': 'Zinc as an adjunct to the treatment of severe pneumonia in Ecuadorian '
'children: a randomized controlled trial',
'volume': '99',
'author': 'Sempértegui',
'year': '2014',
'journal-title': 'Am J Clin Nutr.'},
{ 'key': '10.1111/crj.12646-BIB0008|crj12646-cit-0009',
'doi-asserted-by': 'crossref',
'first-page': '36',
'DOI': '10.1186/1824-7288-38-36',
'article-title': 'Role of zinc in severe pneumonia: a randomized double bind placebo '
'controlled study',
'volume': '38',
'author': 'Shah',
'year': '2012',
'journal-title': 'Ital J Pediatr.'},
{ 'issue': '6',
'key': '10.1111/crj.12646-BIB0009|crj12646-cit-0010',
'doi-asserted-by': 'crossref',
'first-page': '1667',
'DOI': '10.3945/ajcn.2009.28907',
'article-title': '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',
'volume': '91',
'author': 'Valentiner-Branth',
'year': '2010',
'journal-title': 'Am J Clin Nutr.'},
{ 'issue': '6',
'key': '10.1111/crj.12646-BIB0010|crj12646-cit-0011',
'doi-asserted-by': 'crossref',
'first-page': '1387',
'DOI': '10.3945/ajcn.112.052951',
'article-title': 'Efficacy of zinc given as an adjunct in the treatment of severe and '
'very severe pneumonia in hospitalized children 2-24 mo of age: a '
'randomized, double-blind, placebo-controlled trial',
'volume': '97',
'author': 'Wadhwa',
'year': '2013',
'journal-title': 'Am J Clin Nutr.'},
{ 'issue': '4',
'key': '10.1111/crj.12646-BIB0011|crj12646-cit-0012',
'doi-asserted-by': 'crossref',
'first-page': '701',
'DOI': '10.1542/peds.2010-3091',
'article-title': 'A randomized controlled trial of zinc as adjuvant therapy for severe '
'pneumonia in young children',
'volume': '129',
'author': 'Basnet',
'year': '2012',
'journal-title': 'Pediatrics.'},
{ 'key': '10.1111/crj.12646-BIB0012|crj12646-cit-0013',
'doi-asserted-by': 'crossref',
'first-page': '14',
'DOI': '10.1186/1741-7015-10-14',
'article-title': 'Zinc adjunct therapy reduces case fatality in severe childhood '
'pneumonia: a randomized double blind placebo-controlled trial',
'volume': '10',
'author': 'Srinivasan',
'year': '2012',
'journal-title': 'BMC Med.'},
{ 'key': '10.1111/crj.12646-BIB0013|crj12646-cit-0014',
'unstructured': 'Higgins JPT Altman DG Sterne JAC. 2011 http://www.cochrane-handbook.org'},
{ 'issue': '2',
'key': '10.1111/crj.12646-BIB0014|crj12646-cit-0015',
'doi-asserted-by': 'crossref',
'first-page': '67',
'DOI': '10.1016/j.trsl.2008.06.001',
'article-title': 'Zinc supplementation decreases oxidative stress, incidence of '
'infection, and generation of inflammatory cytokines in sickle cell '
'disease patients',
'volume': '152',
'author': 'Bao',
'year': '2008',
'journal-title': 'Transl Res.'},
{ 'issue': '3',
'key': '10.1111/crj.12646-BIB0015|crj12646-cit-0016',
'doi-asserted-by': 'crossref',
'first-page': '444',
'DOI': '10.1093/ajcn/79.3.444',
'article-title': 'Effect of zinc supplementation on immune and inflammatory responses in '
'pediatric patients with shigellosis',
'volume': '79',
'author': 'Raqib',
'year': '2004',
'journal-title': 'Am J Clin Nutr.'},
{ 'issue': '3',
'key': '10.1111/crj.12646-BIB0016|crj12646-cit-0017',
'doi-asserted-by': 'crossref',
'first-page': '602',
'DOI': '10.1093/ajcn/45.3.602',
'article-title': 'Controlled trial of zinc supplementation during recovery from '
'malnutrition: effects on growth and immune function',
'volume': '45',
'author': 'Castillo-Duran',
'year': '1987',
'journal-title': 'Am J Clin Nutr.'},
{ 'issue': '3',
'key': '10.1111/crj.12646-BIB0017|crj12646-cit-0018',
'doi-asserted-by': 'crossref',
'first-page': 'L433',
'DOI': '10.1152/ajplung.00341.2005',
'article-title': 'Zinc modulates airway epithelium susceptibility to death '
'receptor-mediated apoptosis',
'volume': '290',
'author': 'Bao',
'year': '2006',
'journal-title': 'Am J Physiol Lung Cell Mol Physiol.'},
{ 'issue': '5',
'key': '10.1111/crj.12646-BIB0018|crj12646-cit-0019',
'doi-asserted-by': 'crossref',
'first-page': '591',
'DOI': '10.1038/ejcn.2008.9',
'article-title': 'Global and regional child mortality and burden of disease attributable '
'to zinc deficiency',
'volume': '63',
'author': 'Fischer Walker',
'year': '2009',
'journal-title': 'Eur J Clin Nutr.'},
{ 'issue': '11',
'key': '10.1111/crj.12646-BIB0019|crj12646-cit-0020',
'doi-asserted-by': 'crossref',
'first-page': 'e79998',
'DOI': '10.1371/journal.pone.0079998',
'article-title': 'Effects of zinc supplementation on the incidence of mortality in '
'preschool children: a meta-analysis of randomized controlled trials',
'volume': '8',
'author': 'Fu',
'year': '2013',
'journal-title': 'PLoS One.'}],
'container-title': 'The Clinical Respiratory Journal',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fcrj.12646',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'http://onlinelibrary.wiley.com/wol1/doi/10.1111/crj.12646/fullpdf',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 7, 4]],
'date-time': '2021-07-04T22:30:17Z',
'timestamp': 1625437817000},
'score': 1,
'resource': {'primary': {'URL': 'https://onlinelibrary.wiley.com/doi/10.1111/crj.12646'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2017, 5, 31]]},
'references-count': 19,
'journal-issue': {'issue': '3', 'published-print': {'date-parts': [[2018, 3]]}},
'URL': 'http://dx.doi.org/10.1111/crj.12646',
'relation': {},
'ISSN': ['1752-6981'],
'subject': ['Genetics (clinical)', 'Pulmonary and Respiratory Medicine', 'Immunology and Allergy'],
'container-title-short': 'Clin Respir J',
'published': {'date-parts': [[2017, 5, 31]]}}
