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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effects of Fruit and Vegetable Consumption on Risk of Asthma, Wheezing and Immune Responses: A Systematic Review and Meta-Analysis</title>
<author><name sortKey="Hosseini, Banafshe" sort="Hosseini, Banafshe" uniqKey="Hosseini B" first="Banafshe" last="Hosseini">Banafshe Hosseini</name>
<affiliation><nlm:aff id="af1-nutrients-09-00341">School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia;<email>b.hosseini.bh@gmail.com</email>
(B.H.);<email>bronwyn.berthon@newcastle.edu.au</email>
(B.S.B.)</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="af2-nutrients-09-00341">Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, NSW 2308, Australia;<email>Peter.Wark@hnehealth.nsw.gov.au</email>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Berthon, Bronwyn S" sort="Berthon, Bronwyn S" uniqKey="Berthon B" first="Bronwyn S." last="Berthon">Bronwyn S. Berthon</name>
<affiliation><nlm:aff id="af1-nutrients-09-00341">School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia;<email>b.hosseini.bh@gmail.com</email>
(B.H.);<email>bronwyn.berthon@newcastle.edu.au</email>
(B.S.B.)</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="af2-nutrients-09-00341">Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, NSW 2308, Australia;<email>Peter.Wark@hnehealth.nsw.gov.au</email>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wark, Peter" sort="Wark, Peter" uniqKey="Wark P" first="Peter" last="Wark">Peter Wark</name>
<affiliation><nlm:aff id="af2-nutrients-09-00341">Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, NSW 2308, Australia;<email>Peter.Wark@hnehealth.nsw.gov.au</email>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wood, Lisa G" sort="Wood, Lisa G" uniqKey="Wood L" first="Lisa G." last="Wood">Lisa G. Wood</name>
<affiliation><nlm:aff id="af1-nutrients-09-00341">School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia;<email>b.hosseini.bh@gmail.com</email>
(B.H.);<email>bronwyn.berthon@newcastle.edu.au</email>
(B.S.B.)</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="af2-nutrients-09-00341">Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, NSW 2308, Australia;<email>Peter.Wark@hnehealth.nsw.gov.au</email>
</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">28353635</idno>
<idno type="pmc">5409680</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409680</idno>
<idno type="RBID">PMC:5409680</idno>
<idno type="doi">10.3390/nu9040341</idno>
<date when="2017">2017</date>
<idno type="wicri:Area/Pmc/Corpus">000B19</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B19</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Effects of Fruit and Vegetable Consumption on Risk of Asthma, Wheezing and Immune Responses: A Systematic Review and Meta-Analysis</title>
<author><name sortKey="Hosseini, Banafshe" sort="Hosseini, Banafshe" uniqKey="Hosseini B" first="Banafshe" last="Hosseini">Banafshe Hosseini</name>
<affiliation><nlm:aff id="af1-nutrients-09-00341">School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia;<email>b.hosseini.bh@gmail.com</email>
(B.H.);<email>bronwyn.berthon@newcastle.edu.au</email>
(B.S.B.)</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="af2-nutrients-09-00341">Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, NSW 2308, Australia;<email>Peter.Wark@hnehealth.nsw.gov.au</email>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Berthon, Bronwyn S" sort="Berthon, Bronwyn S" uniqKey="Berthon B" first="Bronwyn S." last="Berthon">Bronwyn S. Berthon</name>
<affiliation><nlm:aff id="af1-nutrients-09-00341">School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia;<email>b.hosseini.bh@gmail.com</email>
(B.H.);<email>bronwyn.berthon@newcastle.edu.au</email>
(B.S.B.)</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="af2-nutrients-09-00341">Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, NSW 2308, Australia;<email>Peter.Wark@hnehealth.nsw.gov.au</email>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wark, Peter" sort="Wark, Peter" uniqKey="Wark P" first="Peter" last="Wark">Peter Wark</name>
<affiliation><nlm:aff id="af2-nutrients-09-00341">Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, NSW 2308, Australia;<email>Peter.Wark@hnehealth.nsw.gov.au</email>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wood, Lisa G" sort="Wood, Lisa G" uniqKey="Wood L" first="Lisa G." last="Wood">Lisa G. Wood</name>
<affiliation><nlm:aff id="af1-nutrients-09-00341">School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia;<email>b.hosseini.bh@gmail.com</email>
(B.H.);<email>bronwyn.berthon@newcastle.edu.au</email>
(B.S.B.)</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="af2-nutrients-09-00341">Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, NSW 2308, Australia;<email>Peter.Wark@hnehealth.nsw.gov.au</email>
</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Nutrients</title>
<idno type="eISSN">2072-6643</idno>
<imprint><date when="2017">2017</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Evidence suggests that reduced intake of fruit and vegetables may play a critical role in the development of asthma and allergies. The present review aimed to summarize the evidence for the association between fruit and vegetable intake, risk of asthma/wheeze and immune responses. Databases including PubMed, Cochrane, CINAHL and EMBASE were searched up to June 2016. Studies that investigated the effects of fruit and vegetable intake on risk of asthma/wheeze and immune responses were considered eligible (<italic>n</italic>
= 58). Studies used cross-sectional (<italic>n</italic>
= 30), cohort (<italic>n</italic>
= 13), case-control (<italic>n</italic>
= 8) and experimental (<italic>n</italic>
= 7) designs. Most of the studies (<italic>n</italic>
= 30) reported beneficial associations of fruit and vegetable consumption with risk of asthma and/or respiratory function, while eight studies found no significant relationship. Some studies (<italic>n</italic>
= 20) reported mixed results, as they found a negative association between fruit only or vegetable only, and asthma. In addition, the meta-analyses in both adults and children showed inverse associations between fruit intake and risk of prevalent wheeze and asthma severity (<italic>p</italic>
< 0.05). Likewise, vegetable intake was negatively associated with risk of prevalent asthma (<italic>p</italic>
< 0.05). Seven studies examined immune responses in relation to fruit and vegetable intake in asthma, with <italic>n</italic>
= 6 showing a protective effect against either systemic or airway inflammation. Fruit and vegetable consumption appears to be protective against asthma.</p>
</div>
</front>
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<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Nutrients</journal-id>
<journal-id journal-id-type="iso-abbrev">Nutrients</journal-id>
<journal-id journal-id-type="publisher-id">nutrients</journal-id>
<journal-title-group><journal-title>Nutrients</journal-title>
</journal-title-group>
<issn pub-type="epub">2072-6643</issn>
<publisher><publisher-name>MDPI</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">28353635</article-id>
<article-id pub-id-type="pmc">5409680</article-id>
<article-id pub-id-type="doi">10.3390/nu9040341</article-id>
<article-id pub-id-type="publisher-id">nutrients-09-00341</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Review</subject>
</subj-group>
</article-categories>
<title-group><article-title>Effects of Fruit and Vegetable Consumption on Risk of Asthma, Wheezing and Immune Responses: A Systematic Review and Meta-Analysis</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Hosseini</surname>
<given-names>Banafshe</given-names>
</name>
<xref ref-type="aff" rid="af1-nutrients-09-00341">1</xref>
<xref ref-type="aff" rid="af2-nutrients-09-00341">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Berthon</surname>
<given-names>Bronwyn S.</given-names>
</name>
<xref ref-type="aff" rid="af1-nutrients-09-00341">1</xref>
<xref ref-type="aff" rid="af2-nutrients-09-00341">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wark</surname>
<given-names>Peter</given-names>
</name>
<xref ref-type="aff" rid="af2-nutrients-09-00341">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wood</surname>
<given-names>Lisa G.</given-names>
</name>
<xref ref-type="aff" rid="af1-nutrients-09-00341">1</xref>
<xref ref-type="aff" rid="af2-nutrients-09-00341">2</xref>
<xref rid="c1-nutrients-09-00341" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="af1-nutrients-09-00341"><label>1</label>
School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia;<email>b.hosseini.bh@gmail.com</email>
(B.H.);<email>bronwyn.berthon@newcastle.edu.au</email>
(B.S.B.)</aff>
<aff id="af2-nutrients-09-00341"><label>2</label>
Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, NSW 2308, Australia;<email>Peter.Wark@hnehealth.nsw.gov.au</email>
</aff>
<author-notes><corresp id="c1-nutrients-09-00341"><label>*</label>
Correspondence: <email>lisa.wood@newcastle.edu.au</email>
; Tel.: +61-2-4042-0147; Fax: +61-2-4042-0046</corresp>
</author-notes>
<pub-date pub-type="epub"><day>29</day>
<month>3</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="collection"><month>4</month>
<year>2017</year>
</pub-date>
<volume>9</volume>
<issue>4</issue>
<elocation-id>341</elocation-id>
<history><date date-type="received"><day>08</day>
<month>12</month>
<year>2016</year>
</date>
<date date-type="accepted"><day>24</day>
<month>3</month>
<year>2017</year>
</date>
</history>
<permissions><copyright-statement>© 2017 by the authors.</copyright-statement>
<copyright-year>2017</copyright-year>
<license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
).</license-p>
</license>
</permissions>
<abstract><p>Evidence suggests that reduced intake of fruit and vegetables may play a critical role in the development of asthma and allergies. The present review aimed to summarize the evidence for the association between fruit and vegetable intake, risk of asthma/wheeze and immune responses. Databases including PubMed, Cochrane, CINAHL and EMBASE were searched up to June 2016. Studies that investigated the effects of fruit and vegetable intake on risk of asthma/wheeze and immune responses were considered eligible (<italic>n</italic>
= 58). Studies used cross-sectional (<italic>n</italic>
= 30), cohort (<italic>n</italic>
= 13), case-control (<italic>n</italic>
= 8) and experimental (<italic>n</italic>
= 7) designs. Most of the studies (<italic>n</italic>
= 30) reported beneficial associations of fruit and vegetable consumption with risk of asthma and/or respiratory function, while eight studies found no significant relationship. Some studies (<italic>n</italic>
= 20) reported mixed results, as they found a negative association between fruit only or vegetable only, and asthma. In addition, the meta-analyses in both adults and children showed inverse associations between fruit intake and risk of prevalent wheeze and asthma severity (<italic>p</italic>
< 0.05). Likewise, vegetable intake was negatively associated with risk of prevalent asthma (<italic>p</italic>
< 0.05). Seven studies examined immune responses in relation to fruit and vegetable intake in asthma, with <italic>n</italic>
= 6 showing a protective effect against either systemic or airway inflammation. Fruit and vegetable consumption appears to be protective against asthma.</p>
</abstract>
<kwd-group><kwd>fruit</kwd>
<kwd>vegetable</kwd>
<kwd>antioxidant</kwd>
<kwd>asthma</kwd>
<kwd>wheezing</kwd>
<kwd>immune response</kwd>
</kwd-group>
</article-meta>
</front>
<body><sec id="sec1-nutrients-09-00341"><title>1. Introduction</title>
<p>Asthma is a chronic inflammatory lung disease, associated with airway constriction, inflammation, bronchial hyper-responsiveness (BHR), as well as respiratory symptoms such as coughing, wheezing, dyspnoea and chest tightness. The rise in incidence, prevalence and related medical and economic costs of asthma across all age groups is a public health concern [<xref rid="B1-nutrients-09-00341" ref-type="bibr">1</xref>
]. In Australia, one in every 10 adults has asthma. It has been estimated that currently about 300 million people suffer from asthma worldwide, with 250,000 annual deaths related to the disease. It is also estimated that the prevalence of asthma will grow by more than 100 million by 2025 [<xref rid="B2-nutrients-09-00341" ref-type="bibr">2</xref>
]. Asthma is the consequence of complicated interactions between genetics and environmental factors. In genetically susceptible people, such interactions can lead to the development of airway inflammation, atopy and/or BHR [<xref rid="B3-nutrients-09-00341" ref-type="bibr">3</xref>
]. Environmental factors including tobacco smoke, allergen exposure, pollen, mites, air pollution, chemical sprays, high ozone levels, broad-spectrum antibiotic usage during the first years of life, small size at birth, having few siblings, as well as respiratory infections such as Rhinovirus (RV) can play a major role in developing asthma exacerbations [<xref rid="B4-nutrients-09-00341" ref-type="bibr">4</xref>
,<xref rid="B5-nutrients-09-00341" ref-type="bibr">5</xref>
]. The considerable morbidity related to asthma may be ameliorated by addressing modifiable risk factors such as diet [<xref rid="B6-nutrients-09-00341" ref-type="bibr">6</xref>
]. It has been suggested that the increased prevalence of asthma in recent decades may be associated with changes in dietary habits since the 1950s—particularly, deficiency in dietary antioxidants [<xref rid="B7-nutrients-09-00341" ref-type="bibr">7</xref>
]. The Western diet has shifted towards less fruit and vegetables, and high intakes of convenience foods that are low in fibre and antioxidants and rich in saturated fats [<xref rid="B8-nutrients-09-00341" ref-type="bibr">8</xref>
,<xref rid="B9-nutrients-09-00341" ref-type="bibr">9</xref>
].</p>
<p>Oxidative stress plays a major role in the pathophysiology of asthma, due to chronic activation of airway inflammatory cells [<xref rid="B10-nutrients-09-00341" ref-type="bibr">10</xref>
]. There is ample evidence that oxidative stress can have various deleterious effects on airway function, including airway smooth muscle contraction, induction of BHR, mucus hypersecretion, epithelial shedding and vascular exudation [<xref rid="B11-nutrients-09-00341" ref-type="bibr">11</xref>
,<xref rid="B12-nutrients-09-00341" ref-type="bibr">12</xref>
]. Moreover, reactive oxygen species (ROS) can activate transcription factor nuclear factor-kappa B (NF-κB), which results in a cascade of events involving upregulation of the transcription of various inflammatory cytokine genes, such as interleukin-6 (IL-6) and eventually influx and degranulation of airway neutrophils [<xref rid="B8-nutrients-09-00341" ref-type="bibr">8</xref>
]. Fresh fruit and vegetables provide rich sources of antioxidants and other biologically active substances (such as flavonoids, isoflavonoids and polyphenolic compounds) [<xref rid="B12-nutrients-09-00341" ref-type="bibr">12</xref>
]. Studies have shown that diets with low average consumption of fruit and vegetables play a major role in the development of allergic diseases [<xref rid="B1-nutrients-09-00341" ref-type="bibr">1</xref>
,<xref rid="B7-nutrients-09-00341" ref-type="bibr">7</xref>
], and may augment oxidative stress in asthma [<xref rid="B13-nutrients-09-00341" ref-type="bibr">13</xref>
]. Antioxidants can reduce airway inflammation via protecting the airways against oxidants by both endogenous (activated inflammatory cells) and exogenous (such as air pollution, cigarette smoke) sources [<xref rid="B7-nutrients-09-00341" ref-type="bibr">7</xref>
]. Moreover, dietary antioxidants present in fruit and vegetables can scavenge ROS, and thus inhibit NFκB-mediated inflammation, while diets low in antioxidants have reduced capacity to respond to oxidative stress [<xref rid="B8-nutrients-09-00341" ref-type="bibr">8</xref>
].</p>
<p>Currently available asthma medications, such as glucocorticoids, are ineffective in some cases such as viral-induced exacerbations [<xref rid="B14-nutrients-09-00341" ref-type="bibr">14</xref>
]; and prolonged treatment with these therapeutic agents can result in adverse effects, such as pneumonia, cataracts, and osteoporosis [<xref rid="B15-nutrients-09-00341" ref-type="bibr">15</xref>
]. Therefore, non-pharmacological interventions are required to reduce the burden of asthma in both adults and children. Understanding the roles of dietary nutrients in asthma and asthma-related complications may help in the management of this chronic inflammatory disease. Hence, a systematic review of the intake of fruits and vegetables and their effects on immune responses and asthma risk is of interest. This paper aimed to describe studies investigating the effects of fruit and vegetable consumption on risk of asthma and wheezing and immune responses (including immune responses to virus infection and inflammation) in asthma and wheezing.</p>
</sec>
<sec id="sec2-nutrients-09-00341"><title>2. Methods</title>
<sec id="sec2dot1-nutrients-09-00341"><title>2.1. Search Strategy</title>
<p>PubMed, Cochrane, CINAHL and EMBASE databases were included in the literature search, which was conducted in June 2016, including all previously published articles. Studies were limited to humans with no language restrictions. Additional studies were identified by hand searching references from the identified studies. See <xref ref-type="fig" rid="nutrients-09-00341-f001">Figure 1</xref>
for an example of the search strategy.</p>
</sec>
<sec id="sec2dot2-nutrients-09-00341"><title>2.2. Study Selection</title>
<p>Only original studies with the following designs were included: randomized controlled trials, quasi-experimental studies, cohort studies, case-control studies, before and after studies, and cross sectional studies. Case studies, case reports, animal studies, opinion papers, in vitro studies and conference abstracts were excluded. Review articles were collected for the purposes of reviewing the reference list and did not contribute to the final number of included studies. The target study population was human of all age, gender or ethnicity, with asthma, wheeze, airway inflammation or other related respiratory symptoms. The exposure of interest was intake of whole or extracted fruit and vegetables. The study outcome measures were respiratory virus infection including human rhinovirus, influenza virus, corona virus and adenovirus; markers of systemic inflammation such as ILs, C-reactive protein, tumour necrosis factor-α and intercellular adhesion molecule 1; and related clinical outcomes including respiratory function such as forced expiratory volume in one second (FEV1), forced vital capacity (FVC), asthma control and symptoms such as dyspnoea, coughing, wheezing and chest tightness.</p>
<p>Citations from literature databases were imported into referencing software Endnote X7.7 (Clarivate Analytic, Philadelphia, PA, USA). All studies retrieved by the search strategy were initially assessed for relevance to the review based on the title using inclusion and exclusion criteria. Articles considered not relevant based on title were coded NR (not retrieve) with the reason noted. Articles considered relevant, or unclear were coded R (retrieve). Further assessments of the retrieved articles were according to the abstract, keywords and MeSH terms, using the inclusion and exclusion criteria. Again, articles were coded as either NR with the reason or R. Retrieved full text articles were then assessed for inclusion criteria. If there was doubt as to whether an article met the defined inclusion criteria according to the title, abstract, keywords and MeSH term, the full article was assessed for clarification.</p>
</sec>
<sec id="sec2dot3-nutrients-09-00341"><title>2.3. Study Quality</title>
<p>Eligible studies were assessed in terms of the methodological quality based on a standardised critical appraisal checklist designed by the American Dietetic Association [<xref rid="B16-nutrients-09-00341" ref-type="bibr">16</xref>
]. The tool considered the reliability, validity, as well as generalisability of the included studies. No study was excluded due to poor quality. The two reviewers (BH and BB) then made final decisions on the included studies by cross-checking results. In cases of disagreement on the inclusion of a study, the other independent reviewers decided on the inclusion or exclusion of the study. Studies that were excluded at this stage were recorded with the reason noted.</p>
</sec>
<sec id="sec2dot4-nutrients-09-00341"><title>2.4. Data Extraction and Study Synthesis</title>
<p>Study details were extracted and recorded into a custom-designed database. Data extracted included title, authors, country, study design, participant characteristics, study factor (e.g., dosage/dietary intake of fruits and vegetables), main outcome measures, findings including statistical significance, analysis with adjustment for confounding factors, and limitations.</p>
</sec>
<sec id="sec2dot5-nutrients-09-00341"><title>2.5. Statistical Methods</title>
<p>A meta-analysis was used to evaluate the association between fruit and vegetable intake and risk of asthma and/or wheezing. Only studies that met the following inclusion criteria were included in the meta-analysis: (a) fruit and vegetable intake reported; (b) the odds ratio (OR) or the relative risks and the corresponding 95% confidence intervals (CI) were reported. However, due to the heterogeneity of study designs and differences in exposure and outcome assessments, meta-analysis of all of these studies were not possible. The analysis was performed for the total number of adults and children together, and pregnant women. To assess the risk of asthma and/or wheezing, the risk estimate from each study, weighted by the inverse of variance, was pooled. Appreciable heterogeneity was assumed if <italic>I</italic>
<sup>2</sup>
> 50 and <italic>p</italic>
< 0.1. Meta-analysis was performed using random effect modelling if <italic>I</italic>
<sup>2</sup>
> 50 and fixed effect modelling was used if <italic>I</italic>
<sup>2</sup>
< 50. Most studies assessed dietary intake with a validated food frequency questionnaire (FFQ), and other studies used a dietary habit questionnaire, food diaries or 24 h recall. Some studies used an FFQ with limited fruit and vegetable items such as Rosenlund et al. [<xref rid="B17-nutrients-09-00341" ref-type="bibr">17</xref>
], while other studies used an FFQ which included over 50 items, such as Shaheen et al. [<xref rid="B18-nutrients-09-00341" ref-type="bibr">18</xref>
] (>200 items), Romieu et al. [<xref rid="B19-nutrients-09-00341" ref-type="bibr">19</xref>
] (108 items), and Protudjer et al. [<xref rid="B20-nutrients-09-00341" ref-type="bibr">20</xref>
] (72 items). In addition, some of the FFQs were modified for use in children [<xref rid="B21-nutrients-09-00341" ref-type="bibr">21</xref>
]. Since the included studies used different methods in reporting fruit and vegetable intake (i.e., >4 times/week vs. never, quartile 4 vs. quartile 1, daily intake vs. never, etc.), in order to include more studies in the meta-analysis, two terms were defined: high fruit and/or vegetable intake (the group that had the highest intake of fruit and vegetables in each study) vs. low fruit and/or vegetable intake (the group that had the lowest intake of fruit and vegetables in each study). <xref ref-type="table" rid="nutrients-09-00341-t001">Table 1</xref>
, <xref ref-type="table" rid="nutrients-09-00341-t002">Table 2</xref>
and <xref ref-type="table" rid="nutrients-09-00341-t003">Table 3</xref>
show how the variables are contrasted in different studies.</p>
</sec>
</sec>
<sec id="sec3-nutrients-09-00341"><title>3. Results</title>
<p>Initially, 3194 abstracts were identified by the search strategy. After removing duplicates and screening the titles, 142 articles were retrieved for abstract review. Based on the abstracts, 80 articles were excluded based on outcomes (<italic>n</italic>
= 16), exposures (<italic>n</italic>
= 26) or study design (<italic>n</italic>
= 38). After reviewing the full-texts, five articles were excluded as fruit and vegetable intakes were not reported, and also one study was additionally included during the review process. Finally, Fifty-eight articles were included in the review (<xref ref-type="fig" rid="nutrients-09-00341-f002">Figure 2</xref>
).</p>
<sec id="sec3dot1-nutrients-09-00341"><title>3.1. Characteristics of Included Studies</title>
<p>More than half of the studies were performed in children (<italic>n</italic>
= 28), adolescents (<italic>n</italic>
= 3) or both (<italic>n</italic>
= 10), with only 17 conducted in adults. Cross-sectional design was most commonly used (<xref ref-type="table" rid="nutrients-09-00341-t001">Table 1</xref>
) with 8 case-control studies (<xref ref-type="table" rid="nutrients-09-00341-t002">Table 2</xref>
), 13 cohort studies (<xref ref-type="table" rid="nutrients-09-00341-t003">Table 3</xref>
) and 7 clinical trials (<xref ref-type="table" rid="nutrients-09-00341-t004">Table 4</xref>
). The majority of studies were conducted in UK (<italic>n</italic>
= 8) [<xref rid="B1-nutrients-09-00341" ref-type="bibr">1</xref>
,<xref rid="B18-nutrients-09-00341" ref-type="bibr">18</xref>
,<xref rid="B22-nutrients-09-00341" ref-type="bibr">22</xref>
,<xref rid="B23-nutrients-09-00341" ref-type="bibr">23</xref>
,<xref rid="B24-nutrients-09-00341" ref-type="bibr">24</xref>
,<xref rid="B25-nutrients-09-00341" ref-type="bibr">25</xref>
,<xref rid="B26-nutrients-09-00341" ref-type="bibr">26</xref>
,<xref rid="B27-nutrients-09-00341" ref-type="bibr">27</xref>
], but also in Australia (<italic>n</italic>
= 5) [<xref rid="B28-nutrients-09-00341" ref-type="bibr">28</xref>
,<xref rid="B29-nutrients-09-00341" ref-type="bibr">29</xref>
,<xref rid="B30-nutrients-09-00341" ref-type="bibr">30</xref>
,<xref rid="B31-nutrients-09-00341" ref-type="bibr">31</xref>
,<xref rid="B32-nutrients-09-00341" ref-type="bibr">32</xref>
], Greece (<italic>n</italic>
= 5) [<xref rid="B13-nutrients-09-00341" ref-type="bibr">13</xref>
,<xref rid="B33-nutrients-09-00341" ref-type="bibr">33</xref>
,<xref rid="B34-nutrients-09-00341" ref-type="bibr">34</xref>
,<xref rid="B35-nutrients-09-00341" ref-type="bibr">35</xref>
,<xref rid="B36-nutrients-09-00341" ref-type="bibr">36</xref>
], Spain (<italic>n</italic>
= 4) [<xref rid="B37-nutrients-09-00341" ref-type="bibr">37</xref>
,<xref rid="B38-nutrients-09-00341" ref-type="bibr">38</xref>
,<xref rid="B39-nutrients-09-00341" ref-type="bibr">39</xref>
,<xref rid="B40-nutrients-09-00341" ref-type="bibr">40</xref>
], Italy (<italic>n</italic>
= 4) [<xref rid="B9-nutrients-09-00341" ref-type="bibr">9</xref>
,<xref rid="B41-nutrients-09-00341" ref-type="bibr">41</xref>
,<xref rid="B42-nutrients-09-00341" ref-type="bibr">42</xref>
,<xref rid="B43-nutrients-09-00341" ref-type="bibr">43</xref>
], Brazil (<italic>n</italic>
= 3) [<xref rid="B44-nutrients-09-00341" ref-type="bibr">44</xref>
,<xref rid="B45-nutrients-09-00341" ref-type="bibr">45</xref>
,<xref rid="B46-nutrients-09-00341" ref-type="bibr">46</xref>
], Netherlands (<italic>n</italic>
= 3) [<xref rid="B21-nutrients-09-00341" ref-type="bibr">21</xref>
,<xref rid="B47-nutrients-09-00341" ref-type="bibr">47</xref>
,<xref rid="B48-nutrients-09-00341" ref-type="bibr">48</xref>
], USA (<italic>n</italic>
= 3) [<xref rid="B9-nutrients-09-00341" ref-type="bibr">9</xref>
,<xref rid="B49-nutrients-09-00341" ref-type="bibr">49</xref>
,<xref rid="B50-nutrients-09-00341" ref-type="bibr">50</xref>
], Canada (<italic>n</italic>
= 2) [<xref rid="B20-nutrients-09-00341" ref-type="bibr">20</xref>
,<xref rid="B51-nutrients-09-00341" ref-type="bibr">51</xref>
], Finland (<italic>n</italic>
= 2) [<xref rid="B52-nutrients-09-00341" ref-type="bibr">52</xref>
,<xref rid="B53-nutrients-09-00341" ref-type="bibr">53</xref>
], India (<italic>n</italic>
= 2) [<xref rid="B54-nutrients-09-00341" ref-type="bibr">54</xref>
,<xref rid="B55-nutrients-09-00341" ref-type="bibr">55</xref>
], Japan (<italic>n</italic>
= 2) [<xref rid="B56-nutrients-09-00341" ref-type="bibr">56</xref>
,<xref rid="B57-nutrients-09-00341" ref-type="bibr">57</xref>
], Mexico (<italic>n</italic>
= 2) [<xref rid="B19-nutrients-09-00341" ref-type="bibr">19</xref>
,<xref rid="B58-nutrients-09-00341" ref-type="bibr">58</xref>
] Sweden (<italic>n</italic>
= 2) [<xref rid="B17-nutrients-09-00341" ref-type="bibr">17</xref>
,<xref rid="B59-nutrients-09-00341" ref-type="bibr">59</xref>
], Taiwan [<xref rid="B60-nutrients-09-00341" ref-type="bibr">60</xref>
,<xref rid="B61-nutrients-09-00341" ref-type="bibr">61</xref>
] (<italic>n</italic>
= 2), Albania [<xref rid="B62-nutrients-09-00341" ref-type="bibr">62</xref>
], China [<xref rid="B63-nutrients-09-00341" ref-type="bibr">63</xref>
], Colombia [<xref rid="B64-nutrients-09-00341" ref-type="bibr">64</xref>
], Germany [<xref rid="B7-nutrients-09-00341" ref-type="bibr">7</xref>
], Ireland [<xref rid="B65-nutrients-09-00341" ref-type="bibr">65</xref>
], Norway [<xref rid="B66-nutrients-09-00341" ref-type="bibr">66</xref>
], Portugal [<xref rid="B67-nutrients-09-00341" ref-type="bibr">67</xref>
], Saudi Arabia [<xref rid="B68-nutrients-09-00341" ref-type="bibr">68</xref>
], and Singapore [<xref rid="B69-nutrients-09-00341" ref-type="bibr">69</xref>
]. In addition, one study [<xref rid="B70-nutrients-09-00341" ref-type="bibr">70</xref>
] used data from 20 countries. A total of 496,741 participants were included from cross-sectional studies, 2139 cases and 2739 controls from case-control studies, 105,789 individuals with the mean follow-up of 9.53 years from cohort studies. In total, 7109 participants were included in clinical trials with a mean intervention period of 141 days ranging from 3 to 365 days. The methodological quality of 41 studies was positive, and 16 studies were neutral.</p>
</sec>
<sec id="sec3dot2-nutrients-09-00341"><title>3.2. Studies Conducted in Adults</title>
<p>Four cohort [<xref rid="B22-nutrients-09-00341" ref-type="bibr">22</xref>
,<xref rid="B52-nutrients-09-00341" ref-type="bibr">52</xref>
,<xref rid="B58-nutrients-09-00341" ref-type="bibr">58</xref>
,<xref rid="B59-nutrients-09-00341" ref-type="bibr">59</xref>
], two case-control [<xref rid="B18-nutrients-09-00341" ref-type="bibr">18</xref>
,<xref rid="B23-nutrients-09-00341" ref-type="bibr">23</xref>
], eight cross-sectional studies [<xref rid="B31-nutrients-09-00341" ref-type="bibr">31</xref>
,<xref rid="B32-nutrients-09-00341" ref-type="bibr">32</xref>
,<xref rid="B42-nutrients-09-00341" ref-type="bibr">42</xref>
,<xref rid="B55-nutrients-09-00341" ref-type="bibr">55</xref>
,<xref rid="B57-nutrients-09-00341" ref-type="bibr">57</xref>
,<xref rid="B62-nutrients-09-00341" ref-type="bibr">62</xref>
,<xref rid="B67-nutrients-09-00341" ref-type="bibr">67</xref>
,<xref rid="B69-nutrients-09-00341" ref-type="bibr">69</xref>
] and three experimental trials [<xref rid="B28-nutrients-09-00341" ref-type="bibr">28</xref>
,<xref rid="B29-nutrients-09-00341" ref-type="bibr">29</xref>
,<xref rid="B30-nutrients-09-00341" ref-type="bibr">30</xref>
] assessed the association of fruit and vegetable intake and asthma or asthma-related symptoms in adults. Fruit and vegetable intake was reported to have beneficial associations with wheeze, or asthma in eight studies [<xref rid="B18-nutrients-09-00341" ref-type="bibr">18</xref>
,<xref rid="B22-nutrients-09-00341" ref-type="bibr">22</xref>
,<xref rid="B28-nutrients-09-00341" ref-type="bibr">28</xref>
,<xref rid="B29-nutrients-09-00341" ref-type="bibr">29</xref>
,<xref rid="B42-nutrients-09-00341" ref-type="bibr">42</xref>
,<xref rid="B55-nutrients-09-00341" ref-type="bibr">55</xref>
,<xref rid="B59-nutrients-09-00341" ref-type="bibr">59</xref>
,<xref rid="B62-nutrients-09-00341" ref-type="bibr">62</xref>
]; one study [<xref rid="B69-nutrients-09-00341" ref-type="bibr">69</xref>
] found no significant relationship; and eight studies [<xref rid="B23-nutrients-09-00341" ref-type="bibr">23</xref>
,<xref rid="B30-nutrients-09-00341" ref-type="bibr">30</xref>
,<xref rid="B31-nutrients-09-00341" ref-type="bibr">31</xref>
,<xref rid="B32-nutrients-09-00341" ref-type="bibr">32</xref>
,<xref rid="B52-nutrients-09-00341" ref-type="bibr">52</xref>
,<xref rid="B57-nutrients-09-00341" ref-type="bibr">57</xref>
,<xref rid="B58-nutrients-09-00341" ref-type="bibr">58</xref>
,<xref rid="B67-nutrients-09-00341" ref-type="bibr">67</xref>
] reported mixed results. Most of the studies measured total fruit and vegetable intake; however, one cross-sectional study examined only vegetable intake [<xref rid="B42-nutrients-09-00341" ref-type="bibr">42</xref>
], three cohort studies assessed only fresh fruit intake [<xref rid="B22-nutrients-09-00341" ref-type="bibr">22</xref>
,<xref rid="B59-nutrients-09-00341" ref-type="bibr">59</xref>
], and one study [<xref rid="B52-nutrients-09-00341" ref-type="bibr">52</xref>
] analysed the consumption of orange, apple, grapefruit, onion, white cabbage, berries, and juices.</p>
<sec id="sec3dot2dot1-nutrients-09-00341"><title>3.2.1. Cohort Studies</title>
<p>In terms of prospective studies, two studies [<xref rid="B22-nutrients-09-00341" ref-type="bibr">22</xref>
,<xref rid="B59-nutrients-09-00341" ref-type="bibr">59</xref>
] reported fruit and vegetable intake was inversely associated with asthma. Likewise, Knekt et al. [<xref rid="B52-nutrients-09-00341" ref-type="bibr">52</xref>
] found that higher dietary flavonoid intake (measured by intakes of orange, apple, grapefruit, onion, white cabbage, berries, juices) was associated with lower incidence of asthma. The strongest associations were noted for apple and orange intakes and asthma. Another study [<xref rid="B58-nutrients-09-00341" ref-type="bibr">58</xref>
] reported inverse associations between intakes of tomato, carrots, leafy vegetables and asthma. No cohort studies in adults reported associations between fruit and vegetable intake and immune function in asthma.</p>
</sec>
<sec id="sec3dot2dot2-nutrients-09-00341"><title>3.2.2. Case-Control Studies</title>
<p>Two case-control studies [<xref rid="B18-nutrients-09-00341" ref-type="bibr">18</xref>
,<xref rid="B23-nutrients-09-00341" ref-type="bibr">23</xref>
] reported that fruit and/or vegetables intake was inversely associated with asthma risk in adults. No case-control studies in adults reported associations between fruit and vegetable intake and immune function in asthma.</p>
</sec>
<sec id="sec3dot2dot3-nutrients-09-00341"><title>3.2.3. Cross-Sectional Studies </title>
<p>In line with these findings, a cross-sectional study by La vecchia et al. [<xref rid="B42-nutrients-09-00341" ref-type="bibr">42</xref>
] reported that vegetable consumption was inversely associated with bronchial asthma. While Priftanji et al. [<xref rid="B62-nutrients-09-00341" ref-type="bibr">62</xref>
] reported that fruit and vegetable intake between meals can have protective effects against possible allergic asthma. Another cross-sectional study [<xref rid="B31-nutrients-09-00341" ref-type="bibr">31</xref>
] showed that apple and pear intake was inversely associated with current asthma, ever asthma, and BHR, and no significant association was observed regarding vegetable intake and asthma. In contrast, another cross-sectional study [<xref rid="B69-nutrients-09-00341" ref-type="bibr">69</xref>
] failed to observe any significant association between fruit and vegetable intake and FEV<sub>1</sub>
and FVC. Barros et al. [<xref rid="B67-nutrients-09-00341" ref-type="bibr">67</xref>
] found no significant associations between fruit and vegetable intake and exhaled nitric oxide (F<sub>E</sub>
NO) in adults.</p>
</sec>
<sec id="sec3dot2dot4-nutrients-09-00341"><title>3.2.4. Experimental Trial</title>
<p>We have previously investigated the effects on both lung function and airway inflammation following a LOA (low antioxidant) diet, which involved restriction of dietary fruit and vegetable intake [<xref rid="B28-nutrients-09-00341" ref-type="bibr">28</xref>
]. FEV<sub>1</sub>
and FVC % predicted values decreased (<italic>p</italic>
< 0.01) and sputum neutrophils % increased (<italic>p</italic>
< 0.05) following the diet. The study also reported that treatment with tomato juice and tomato extract reduced airway neutrophils and sputum neutrophil elastase activity. Similarly, Baines et al. [<xref rid="B29-nutrients-09-00341" ref-type="bibr">29</xref>
] showed that antioxidant withdrawal, via fruit and vegetable restriction, leads to upregulation of genes involved in the inflammatory and immune responses including the innate immune receptors TLR2, IL1R2, CD93, ANTXR2, and the innate immune signalling molecules IRAK2, 3, MAP3K8 and neutrophil proteases. In another trial [<xref rid="B30-nutrients-09-00341" ref-type="bibr">30</xref>
], we found that subjects on a LAO diet (involving fruit and vegetable restriction) were 2.26 times as likely to have an asthma exacerbation at any time in comparison with the high antioxidant diet group. Lung function also decreased following antioxidant withdrawal in this study. There were no improvements in airway and systemic inflammation, lung function and asthma control after tomato extract supplementation in this study.</p>
</sec>
</sec>
<sec id="sec3dot3-nutrients-09-00341"><title>3.3. Studies Conducted in Children and Adolescents</title>
<p>Forty-one studies including nine cohort [<xref rid="B21-nutrients-09-00341" ref-type="bibr">21</xref>
,<xref rid="B33-nutrients-09-00341" ref-type="bibr">33</xref>
,<xref rid="B37-nutrients-09-00341" ref-type="bibr">37</xref>
,<xref rid="B41-nutrients-09-00341" ref-type="bibr">41</xref>
,<xref rid="B47-nutrients-09-00341" ref-type="bibr">47</xref>
,<xref rid="B48-nutrients-09-00341" ref-type="bibr">48</xref>
,<xref rid="B53-nutrients-09-00341" ref-type="bibr">53</xref>
,<xref rid="B56-nutrients-09-00341" ref-type="bibr">56</xref>
,<xref rid="B65-nutrients-09-00341" ref-type="bibr">65</xref>
], six case-control [<xref rid="B19-nutrients-09-00341" ref-type="bibr">19</xref>
,<xref rid="B20-nutrients-09-00341" ref-type="bibr">20</xref>
,<xref rid="B44-nutrients-09-00341" ref-type="bibr">44</xref>
,<xref rid="B45-nutrients-09-00341" ref-type="bibr">45</xref>
,<xref rid="B49-nutrients-09-00341" ref-type="bibr">49</xref>
,<xref rid="B68-nutrients-09-00341" ref-type="bibr">68</xref>
], 22 cross-sectional studies [<xref rid="B1-nutrients-09-00341" ref-type="bibr">1</xref>
,<xref rid="B7-nutrients-09-00341" ref-type="bibr">7</xref>
,<xref rid="B9-nutrients-09-00341" ref-type="bibr">9</xref>
,<xref rid="B13-nutrients-09-00341" ref-type="bibr">13</xref>
,<xref rid="B17-nutrients-09-00341" ref-type="bibr">17</xref>
,<xref rid="B26-nutrients-09-00341" ref-type="bibr">26</xref>
,<xref rid="B27-nutrients-09-00341" ref-type="bibr">27</xref>
,<xref rid="B34-nutrients-09-00341" ref-type="bibr">34</xref>
,<xref rid="B35-nutrients-09-00341" ref-type="bibr">35</xref>
,<xref rid="B36-nutrients-09-00341" ref-type="bibr">36</xref>
,<xref rid="B39-nutrients-09-00341" ref-type="bibr">39</xref>
,<xref rid="B40-nutrients-09-00341" ref-type="bibr">40</xref>
,<xref rid="B43-nutrients-09-00341" ref-type="bibr">43</xref>
,<xref rid="B46-nutrients-09-00341" ref-type="bibr">46</xref>
,<xref rid="B50-nutrients-09-00341" ref-type="bibr">50</xref>
,<xref rid="B51-nutrients-09-00341" ref-type="bibr">51</xref>
,<xref rid="B54-nutrients-09-00341" ref-type="bibr">54</xref>
,<xref rid="B61-nutrients-09-00341" ref-type="bibr">61</xref>
,<xref rid="B63-nutrients-09-00341" ref-type="bibr">63</xref>
,<xref rid="B64-nutrients-09-00341" ref-type="bibr">64</xref>
,<xref rid="B66-nutrients-09-00341" ref-type="bibr">66</xref>
,<xref rid="B70-nutrients-09-00341" ref-type="bibr">70</xref>
], and four experimental trials [<xref rid="B24-nutrients-09-00341" ref-type="bibr">24</xref>
,<xref rid="B25-nutrients-09-00341" ref-type="bibr">25</xref>
,<xref rid="B38-nutrients-09-00341" ref-type="bibr">38</xref>
,<xref rid="B60-nutrients-09-00341" ref-type="bibr">60</xref>
] assessed the effects of fruit and vegetable intake on asthma or asthma-related symptoms in children and adolescents. An inverse association of fruit and vegetable intake and asthma or wheeze was reported in 22 studies [<xref rid="B1-nutrients-09-00341" ref-type="bibr">1</xref>
,<xref rid="B9-nutrients-09-00341" ref-type="bibr">9</xref>
,<xref rid="B13-nutrients-09-00341" ref-type="bibr">13</xref>
,<xref rid="B19-nutrients-09-00341" ref-type="bibr">19</xref>
,<xref rid="B21-nutrients-09-00341" ref-type="bibr">21</xref>
,<xref rid="B26-nutrients-09-00341" ref-type="bibr">26</xref>
,<xref rid="B33-nutrients-09-00341" ref-type="bibr">33</xref>
,<xref rid="B35-nutrients-09-00341" ref-type="bibr">35</xref>
,<xref rid="B38-nutrients-09-00341" ref-type="bibr">38</xref>
,<xref rid="B39-nutrients-09-00341" ref-type="bibr">39</xref>
,<xref rid="B41-nutrients-09-00341" ref-type="bibr">41</xref>
,<xref rid="B43-nutrients-09-00341" ref-type="bibr">43</xref>
,<xref rid="B45-nutrients-09-00341" ref-type="bibr">45</xref>
,<xref rid="B49-nutrients-09-00341" ref-type="bibr">49</xref>
,<xref rid="B50-nutrients-09-00341" ref-type="bibr">50</xref>
,<xref rid="B54-nutrients-09-00341" ref-type="bibr">54</xref>
,<xref rid="B60-nutrients-09-00341" ref-type="bibr">60</xref>
,<xref rid="B63-nutrients-09-00341" ref-type="bibr">63</xref>
,<xref rid="B65-nutrients-09-00341" ref-type="bibr">65</xref>
,<xref rid="B66-nutrients-09-00341" ref-type="bibr">66</xref>
,<xref rid="B70-nutrients-09-00341" ref-type="bibr">70</xref>
,<xref rid="B71-nutrients-09-00341" ref-type="bibr">71</xref>
], while seven studies [<xref rid="B7-nutrients-09-00341" ref-type="bibr">7</xref>
,<xref rid="B24-nutrients-09-00341" ref-type="bibr">24</xref>
,<xref rid="B27-nutrients-09-00341" ref-type="bibr">27</xref>
,<xref rid="B34-nutrients-09-00341" ref-type="bibr">34</xref>
,<xref rid="B36-nutrients-09-00341" ref-type="bibr">36</xref>
,<xref rid="B53-nutrients-09-00341" ref-type="bibr">53</xref>
,<xref rid="B56-nutrients-09-00341" ref-type="bibr">56</xref>
] did not observe any significant association. Twelve studies [<xref rid="B17-nutrients-09-00341" ref-type="bibr">17</xref>
,<xref rid="B20-nutrients-09-00341" ref-type="bibr">20</xref>
,<xref rid="B37-nutrients-09-00341" ref-type="bibr">37</xref>
,<xref rid="B40-nutrients-09-00341" ref-type="bibr">40</xref>
,<xref rid="B44-nutrients-09-00341" ref-type="bibr">44</xref>
,<xref rid="B46-nutrients-09-00341" ref-type="bibr">46</xref>
,<xref rid="B47-nutrients-09-00341" ref-type="bibr">47</xref>
,<xref rid="B48-nutrients-09-00341" ref-type="bibr">48</xref>
,<xref rid="B51-nutrients-09-00341" ref-type="bibr">51</xref>
,<xref rid="B61-nutrients-09-00341" ref-type="bibr">61</xref>
,<xref rid="B64-nutrients-09-00341" ref-type="bibr">64</xref>
,<xref rid="B68-nutrients-09-00341" ref-type="bibr">68</xref>
] found mixed results. Four studies [<xref rid="B9-nutrients-09-00341" ref-type="bibr">9</xref>
,<xref rid="B19-nutrients-09-00341" ref-type="bibr">19</xref>
,<xref rid="B25-nutrients-09-00341" ref-type="bibr">25</xref>
,<xref rid="B49-nutrients-09-00341" ref-type="bibr">49</xref>
] reported on immune responses to fruit and vegetable intake in children in relation to asthma, with all studies showing a protective effect on systemic or airway inflammation. The majority of studies analysed total fruit and vegetable intake, though five cross-sectional studies assessed the consumption of fruit only [<xref rid="B1-nutrients-09-00341" ref-type="bibr">1</xref>
,<xref rid="B27-nutrients-09-00341" ref-type="bibr">27</xref>
,<xref rid="B43-nutrients-09-00341" ref-type="bibr">43</xref>
,<xref rid="B64-nutrients-09-00341" ref-type="bibr">64</xref>
] or citrus fruit plus vegetables [<xref rid="B7-nutrients-09-00341" ref-type="bibr">7</xref>
]. Additionally, one cohort study [<xref rid="B41-nutrients-09-00341" ref-type="bibr">41</xref>
] assessed the intake of cooked vegetables, salads, tomatoes, fresh fruit, citrus fruit and kiwi, and one birth cohort study [<xref rid="B53-nutrients-09-00341" ref-type="bibr">53</xref>
] measured food-based antioxidant intake.</p>
<sec id="sec3dot3dot1-nutrients-09-00341"><title>3.3.1. Cohort Studies</title>
<p>In a one-year prospective study [<xref rid="B41-nutrients-09-00341" ref-type="bibr">41</xref>
], intake of tomatoes and all fruits and citrus fruit alone had a protective effect on shortness of breath. Similarly, a cohort study [<xref rid="B33-nutrients-09-00341" ref-type="bibr">33</xref>
] that followed children from birth up to 18 years of age reported that daily consumption of fruit and vegetables over the last 12 months was inversely associated with current asthma at 18 years. Another birth cohort study [<xref rid="B48-nutrients-09-00341" ref-type="bibr">48</xref>
] showed that intakes of fresh fruit were inversely associated with asthma symptoms, while, no significant association was observed between cooked vegetable intake and asthma symptoms. No cohort studies in children reported associations between fruit and vegetable intake and immune function in asthma</p>
<p>Four cohort studies addressed the association between maternal fruit and vegetable intake during pregnancy and risk of asthma-related outcomes in their children. One study [<xref rid="B65-nutrients-09-00341" ref-type="bibr">65</xref>
] reported an inverse association between asthma incidence in children and maternal fruit and vegetable intake in pregnancy. Another study [<xref rid="B21-nutrients-09-00341" ref-type="bibr">21</xref>
] reported that maternal apple intake had protective effects on ever wheeze, ever asthma, and doctor-confirmed asthma in the children; however, no consistent associations were observed between childhood outcomes and maternal vegetable consumption. In contrast, a study conducted by Chatzi et al. [<xref rid="B37-nutrients-09-00341" ref-type="bibr">37</xref>
] showed that consumption of vegetables more than eight times per week was inversely correlated with persistent wheeze, while, no association was found regarding fruit intake and wheeze. Two studies [<xref rid="B53-nutrients-09-00341" ref-type="bibr">53</xref>
,<xref rid="B56-nutrients-09-00341" ref-type="bibr">56</xref>
] found no significant association regarding maternal fruit or vegetable intake and risk of wheeze in the offspring. Willers et al. [<xref rid="B47-nutrients-09-00341" ref-type="bibr">47</xref>
] demonstrated that fruit intake had a borderline significant association with wheeze. This study also reported that vegetable intake was positively associated with asthma symptoms in children. </p>
</sec>
<sec id="sec3dot3dot2-nutrients-09-00341"><title>3.3.2. Case-Control Studies</title>
<p>In terms of case-control studies, four studies [<xref rid="B20-nutrients-09-00341" ref-type="bibr">20</xref>
,<xref rid="B44-nutrients-09-00341" ref-type="bibr">44</xref>
,<xref rid="B49-nutrients-09-00341" ref-type="bibr">49</xref>
,<xref rid="B68-nutrients-09-00341" ref-type="bibr">68</xref>
] reported that consumption of vegetables was negatively associated with odds of asthma; however, no difference was observed regarding fruit intake among the groups. In contrast, one study [<xref rid="B45-nutrients-09-00341" ref-type="bibr">45</xref>
] found that regular consumption of fruit in the last month was associated with lower risk of having persistent asthma, while there was no difference in vegetable consumption between the two groups. A follow-up case-control study by Romieu et al. [<xref rid="B19-nutrients-09-00341" ref-type="bibr">19</xref>
] reported that the fruit and vegetable index (FVI) was positively related to FEV<sub>1</sub>
and FVC. A 1-point increase in FVI was associated with a 105 mL (nearly 5%) increase in FVC. For each one-unit increase in FVI there was a significant decrease in IL-8 levels in nasal lavage. Similarly, a recent study [<xref rid="B49-nutrients-09-00341" ref-type="bibr">49</xref>
] reported that increased vegetable consumption is negatively associated with serum IL-17F.</p>
</sec>
<sec id="sec3dot3dot3-nutrients-09-00341"><title>3.3.3. Cross-Sectional Studies</title>
<p>The majority of cross-sectional studies reported beneficial associations of fruit and vegetable intake with lung function (FEV<sub>1</sub>
and FVC) [<xref rid="B26-nutrients-09-00341" ref-type="bibr">26</xref>
,<xref rid="B50-nutrients-09-00341" ref-type="bibr">50</xref>
], wheeze [<xref rid="B13-nutrients-09-00341" ref-type="bibr">13</xref>
,<xref rid="B35-nutrients-09-00341" ref-type="bibr">35</xref>
,<xref rid="B43-nutrients-09-00341" ref-type="bibr">43</xref>
,<xref rid="B54-nutrients-09-00341" ref-type="bibr">54</xref>
] and asthma [<xref rid="B1-nutrients-09-00341" ref-type="bibr">1</xref>
,<xref rid="B9-nutrients-09-00341" ref-type="bibr">9</xref>
,<xref rid="B39-nutrients-09-00341" ref-type="bibr">39</xref>
,<xref rid="B63-nutrients-09-00341" ref-type="bibr">63</xref>
,<xref rid="B66-nutrients-09-00341" ref-type="bibr">66</xref>
] as well as with F<sub>E</sub>
NO levels [<xref rid="B9-nutrients-09-00341" ref-type="bibr">9</xref>
] as a marker of eosinophilic airway inflammation. However, some studies did not observe any association between fruit and vegetable intake and asthma in children [<xref rid="B7-nutrients-09-00341" ref-type="bibr">7</xref>
,<xref rid="B17-nutrients-09-00341" ref-type="bibr">17</xref>
,<xref rid="B27-nutrients-09-00341" ref-type="bibr">27</xref>
,<xref rid="B36-nutrients-09-00341" ref-type="bibr">36</xref>
]. Several cross-sectional studies found an inverse association between vegetable consumption and asthma-related symptoms, although, they did not observe any significant association regarding fruit intake and asthma [<xref rid="B37-nutrients-09-00341" ref-type="bibr">37</xref>
,<xref rid="B40-nutrients-09-00341" ref-type="bibr">40</xref>
,<xref rid="B51-nutrients-09-00341" ref-type="bibr">51</xref>
,<xref rid="B61-nutrients-09-00341" ref-type="bibr">61</xref>
]. In contrast, a recent study [<xref rid="B46-nutrients-09-00341" ref-type="bibr">46</xref>
] reported fruit intake was inversely related to odds of asthma, while, no association was found between vegetable intake and asthma. Garcia et al. [<xref rid="B64-nutrients-09-00341" ref-type="bibr">64</xref>
] found a negative association between fruit intake and asthma in adolescents. An international study of 20 countries [<xref rid="B70-nutrients-09-00341" ref-type="bibr">70</xref>
] reported consumption of cooked green vegetables and raw green vegetables was significantly associated with fewer wheezers in non-affluent countries, and fruit intake was associated with a low prevalence of current wheeze in affluent and non-affluent countries.</p>
</sec>
<sec id="sec3dot3dot4-nutrients-09-00341"><title>3.3.4. Experimental Studies</title>
<p>Lee et al. [<xref rid="B60-nutrients-09-00341" ref-type="bibr">60</xref>
] described a 16-week trial of 192 children with asthma who received fruit and vegetable capsules + fish oil + probiotic vs. placebo and reported the supplement group had a significantly higher increase in FEV<sub>1</sub>
, FVC and FEV<sub>1</sub>
:FVC ratio compared to placebo. The proportion of children using inhaled glucocorticoids decreased following the supplementation, though increased in the placebo group. In another trial by Garcia et al. [<xref rid="B25-nutrients-09-00341" ref-type="bibr">25</xref>
] 32 asthmatic children were randomly allocated to one of four groups: having an apple or a banana or an apple + banana in addition to their normal diet, or the control group (usual diet). The study reported 18% lower FeNO levels in Groups 2 (adding banana) and 3 (adding banana + apple) following the intervention. In a study by Calatayud et al. [<xref rid="B38-nutrients-09-00341" ref-type="bibr">38</xref>
], 104 children aged 1–5 years with current asthma participated in a nutritional education programme based on the traditional Mediterranean diet for one year. The authors reported that fruit and vegetable intake increased significantly with a concomitant decrease in inhaled glucocorticoids use. In contrast, a one-year trial by Fogarty et al. [<xref rid="B24-nutrients-09-00341" ref-type="bibr">24</xref>
] conducted in asthmatic children found that there was no difference in the prevalence of wheezing, exercise-induced wheeze, or nocturnal cough between children who were instructed to add an extra piece of fruit to their diet compared to the control group. </p>
</sec>
</sec>
<sec id="sec3dot4-nutrients-09-00341"><title>3.4. Findings from Meta-Analysis</title>
<p>Primary prevention studies that reported the OR associated with the risk of prevalent asthma/wheeze were analysed separately to secondary prevention studies that reported the OR associated with asthma severity (<italic>n</italic>
= 2) or wheeze severity (<italic>n</italic>
= 1). Meta-analyses of 17 primary prevention studies revealed no significant association between fruit intake and risk of prevalent asthma (OR = 0.98; 95% CI: 0.96–1.0, <italic>p</italic>
= 0.09, <italic>I</italic>
<sup>2</sup>
= 8) (<xref ref-type="fig" rid="nutrients-09-00341-f003">Figure 3</xref>
). However, intake of fruit was inversely associated with the severity of asthma in secondary prevention studies [<xref rid="B45-nutrients-09-00341" ref-type="bibr">45</xref>
,<xref rid="B67-nutrients-09-00341" ref-type="bibr">67</xref>
] (OR = 0.61; 95% CI: 0.44–0.87, <italic>p</italic>
= 0.005, <italic>I</italic>
<sup>2</sup>
= 0) (<xref ref-type="fig" rid="nutrients-09-00341-f004">Figure 4</xref>
). Vegetable intake was negatively related to the prevalence of asthma (OR = 0.95; 95% CI: 0.92–0.98, <italic>p</italic>
= 0.003, <italic>I</italic>
<sup>2</sup>
= 8) (<xref ref-type="fig" rid="nutrients-09-00341-f005">Figure 5</xref>
), while it was not related to the severity of asthma in secondary prevention studies [<xref rid="B45-nutrients-09-00341" ref-type="bibr">45</xref>
,<xref rid="B67-nutrients-09-00341" ref-type="bibr">67</xref>
] (OR = 1.11; 95% CI: 0.63–1.94, <italic>p</italic>
= 0.72, <italic>I</italic>
<sup>2</sup>
= 0) (<xref ref-type="fig" rid="nutrients-09-00341-f006">Figure 6</xref>
). Fruit intake was also negatively associated with risk of prevalent wheeze (OR = 0.94; 95% CI: 0.91–0.97, <italic>p</italic>
< 0.0001, <italic>I</italic>
<sup>2</sup>
= 0%) (<xref ref-type="fig" rid="nutrients-09-00341-f007">Figure 7</xref>
). However, no significant relationship was found between vegetable intake and risk of prevalent wheeze (OR = 0.98; 95% CI: 0.94–1.03, <italic>p</italic>
= 0.41, <italic>I</italic>
<sup>2</sup>
= 0%) (<xref ref-type="fig" rid="nutrients-09-00341-f008">Figure 8</xref>
). Meta-analysis of the association between total fruit and total vegetable intake with the severity of wheeze was not possible as there was only one secondary prevention study [<xref rid="B37-nutrients-09-00341" ref-type="bibr">37</xref>
]. A meta-analysis of six primary prevention studies that reported fruit and vegetable intake together showed no significant relationship with the risk of prevalent asthma (OR = 0.90; 95% CI: 0.80–1.01, <italic>p</italic>
= 0.07, <italic>I</italic>
<sup>2</sup>
= 65%) (<xref ref-type="fig" rid="nutrients-09-00341-f009">Figure 9</xref>
). No meta-analysis was possible for immune markers as well as respiratory infection, due to the lack of available studies. Moreover, meta-analysis on the association between fruit and/or vegetable intake and respiratory function was not possible, as studies used heterogeneous methods in reporting these outcomes.</p>
</sec>
</sec>
<sec id="sec4-nutrients-09-00341"><title>4. Discussion</title>
<p>This systematic review and meta-analysis is the first aimed at investigating the effects of fruit and vegetable consumption on risk of asthma and wheezing and immune responses (including immune responses to virus infection and inflammation) in asthma and wheezing. We found that the majority of studies (<italic>n</italic>
= 8 in adults and <italic>n</italic>
= 22 in children) reported a protective effect of a high fruit and vegetable diet on asthma and/or wheeze. Twenty studies (<italic>n</italic>
= 8 in adults and <italic>n</italic>
= 12 in children) reported mixed results, as they found a negative association between intake of fruit only or vegetable only and risk of asthma and/or wheeze. Eight studies (<italic>n</italic>
= 1 in adults and <italic>n</italic>
= 7 in children) failed to show any beneficial effects of fruit and vegetable intakes on risk of asthma and wheeze. In the meta-analysis, fruit intake was not associated with the risk of prevalent asthma (<italic>p</italic>
> 0.05); however, a negative relationship was observed between consumption of fruit and asthma severity. Intake of vegetables was inversely associated with the prevalence of asthma, while there was no association in secondary prevention studies. In addition, fruit intake was negatively associated with the risk of prevalent wheeze, while no significant relationship was found between vegetable consumption and wheeze prevalence. Fruit and vegetable intake together showed no significant relationship with the risk of prevalent asthma. Meta-analyses of immune response parameters and respiratory infections were not possible due to lack of studies reporting on these markers. </p>
<p>Several mechanisms for the protective effects of fruit and vegetables on asthma and lung function have been suggested. Fresh fruit and vegetables are rich dietary sources of antioxidants such as vitamin C, E and β-carotene as well as flavonoids, isoflavonoids and polyphenolic compounds [<xref rid="B1-nutrients-09-00341" ref-type="bibr">1</xref>
,<xref rid="B7-nutrients-09-00341" ref-type="bibr">7</xref>
]. It has been reported that oxidative stress is elevated in asthma and increases further during acute asthma exacerbations [<xref rid="B72-nutrients-09-00341" ref-type="bibr">72</xref>
,<xref rid="B73-nutrients-09-00341" ref-type="bibr">73</xref>
,<xref rid="B74-nutrients-09-00341" ref-type="bibr">74</xref>
], so a high intake of antioxidants may be beneficial. Vitamin C is a major antioxidant in the extracellular respiratory lining fluid that protects immune cells from oxidative stress, and may also contribute to lung growth and development and reduce airway hyper-reactivity, both of which are determinants of childhood and adult lung function [<xref rid="B50-nutrients-09-00341" ref-type="bibr">50</xref>
]. The potential for vitamin C to prevent asthma-related outcomes is illustrated by a cross-sectional study that documents the protective effects of dietary vitamin C against wheezing and shortness of breath [<xref rid="B43-nutrients-09-00341" ref-type="bibr">43</xref>
]. Vitamin E can be found in various fruits and vegetables, including corn, tomato, spinach, broccoli, kiwifruit, and mango [<xref rid="B75-nutrients-09-00341" ref-type="bibr">75</xref>
]. One study reported that consumption of vitamin E was negatively correlated with forced expiratory flow, which is a measure of small airway flow [<xref rid="B50-nutrients-09-00341" ref-type="bibr">50</xref>
]. Another group of low molecular weight antioxidants found in fruits and vegetables are carotenoids. Lycopene, present in high concentrations in tomatoes, red fruits, watermelons, apricots and pink grapefruit, is the most potent antioxidant among the carotenoids [<xref rid="B76-nutrients-09-00341" ref-type="bibr">76</xref>
]. It has been suggested that oral intakes of lycopene reduce both oxidative stress and the pathophysiological features of asthma such as airway smooth muscle contraction, induction of BHR, and mucus hypersecretion [<xref rid="B76-nutrients-09-00341" ref-type="bibr">76</xref>
]. Flavonoids are a group of polyphenols found in fruits and vegetables that have potent antioxidant as well as anti-inflammatory effects. One study showed that the incidence of asthma was lower at higher total intakes of flavonoids [<xref rid="B52-nutrients-09-00341" ref-type="bibr">52</xref>
]. Moreover, it has been reported that a specific type of flavonoid, called “khellin”, was used traditionally in asthma treatment because of its bronchodilator activity [<xref rid="B52-nutrients-09-00341" ref-type="bibr">52</xref>
]. It is likely that the positive effects of fruit and vegetables can be attributed to the combination of these nutrients, which are present in high concentrations in this natural food source. Moreover, evidence indicates that paediatric asthma, which is allergic in 80% of cases [<xref rid="B77-nutrients-09-00341" ref-type="bibr">77</xref>
], may benefit from fruit and vegetable intake, as several studies reported lower rates of wheezing and allergic rhinitis in children who consumed antioxidant-rich foods daily [<xref rid="B36-nutrients-09-00341" ref-type="bibr">36</xref>
,<xref rid="B48-nutrients-09-00341" ref-type="bibr">48</xref>
,<xref rid="B78-nutrients-09-00341" ref-type="bibr">78</xref>
]. Similarly, high antioxidant intake is related to enhanced pulmonary function and reduced chronic respiratory symptoms in children, especially those exposed to high amounts of air or smoke pollution [<xref rid="B36-nutrients-09-00341" ref-type="bibr">36</xref>
]. Studies also suggest that antioxidants might affect immune function and allergic reactions [<xref rid="B36-nutrients-09-00341" ref-type="bibr">36</xref>
,<xref rid="B78-nutrients-09-00341" ref-type="bibr">78</xref>
]. A study of school-aged children [<xref rid="B79-nutrients-09-00341" ref-type="bibr">79</xref>
] reported that asthma and allergic rhinitis were inversely correlated with serum levels of antioxidants compared to healthy children. Similar results were also observed in adults [<xref rid="B80-nutrients-09-00341" ref-type="bibr">80</xref>
].</p>
<p>This systematic review has highlighted the lack of available data regarding the effects of fruit and vegetable intake on immune responses in asthma. Asthma is a chronic inflammatory disease, involving activation of a variety of immune cell types and increased oxidative stress. Oxidative stress occurs in asthma due to the excessive release of free radicals from activated inflammatory cells and is regarded as one of the critical factors involved in the chronic inflammatory process in both the airways and in the systemic circulation of asthmatics [<xref rid="B9-nutrients-09-00341" ref-type="bibr">9</xref>
,<xref rid="B11-nutrients-09-00341" ref-type="bibr">11</xref>
,<xref rid="B74-nutrients-09-00341" ref-type="bibr">74</xref>
]. Viral respiratory infections are a key contributor to inflammation and oxidative stress in asthma and it has been shown that innate immune responses are impaired in asthmatic adults and children [<xref rid="B81-nutrients-09-00341" ref-type="bibr">81</xref>
], therefore, patients with asthma are more vulnerable to virus infections compared with non-asthmatic controls [<xref rid="B81-nutrients-09-00341" ref-type="bibr">81</xref>
,<xref rid="B82-nutrients-09-00341" ref-type="bibr">82</xref>
]. Consequently, food such as fruits and vegetables, which have the potential to reduce inflammation and oxidative stress due to their anti-inflammatory and anti-oxidative properties, may be beneficial in asthma. Data from three observational studies [<xref rid="B9-nutrients-09-00341" ref-type="bibr">9</xref>
,<xref rid="B19-nutrients-09-00341" ref-type="bibr">19</xref>
,<xref rid="B49-nutrients-09-00341" ref-type="bibr">49</xref>
] in children examined the association between fruit and vegetable intake and inflammation. In each case, there was an association between airway and/or systematic inflammation and intake of fruit and/or vegetable. A cross-sectional study by Cardinale et al. [<xref rid="B9-nutrients-09-00341" ref-type="bibr">9</xref>
] reported that salad intake was negatively associated with F<sub>E</sub>
NO levels. Similarly, an inverse association between fruit and vegetable intake and IL-8 levels in nasal lavage [<xref rid="B19-nutrients-09-00341" ref-type="bibr">19</xref>
], and between vegetable intake and serum IL-17F [<xref rid="B49-nutrients-09-00341" ref-type="bibr">49</xref>
] was reported by two case-control studies. Only one intervention study in children [<xref rid="B25-nutrients-09-00341" ref-type="bibr">25</xref>
] has examined effects of fruit on inflammation, and reported that having a banana or a banana and apple for one month resulted in a statistically significant 18% reduction in F<sub>E</sub>
NO levels. However, fruit and vegetable intake was not related to F<sub>E</sub>
NO levels in adults [<xref rid="B67-nutrients-09-00341" ref-type="bibr">67</xref>
]. In addition, two intervention studies have examined the effect of withdrawal of antioxidant-rich foods (in particular fruit and vegetables) from the diet, on immune responses in adults with asthma [<xref rid="B28-nutrients-09-00341" ref-type="bibr">28</xref>
,<xref rid="B30-nutrients-09-00341" ref-type="bibr">30</xref>
]. In one study, antioxidant withdrawal resulted in increased airway neutrophils [<xref rid="B28-nutrients-09-00341" ref-type="bibr">28</xref>
] and upregulation of inflammatory and immune response genes in sputum cells, including the innate immune receptors TLR2, IL1R2, CD93, ANTXR2, the innate immune signalling molecules IRAK2, IRAK3, MAP3K8 and neutrophil proteases MMP25 and CPD [<xref rid="B29-nutrients-09-00341" ref-type="bibr">29</xref>
]. The major dietary change in these studies was a decrease in fruit and vegetable consumption to a level, which is representative of the typical western diet, which is alarming considering the negative consequences in the airways [<xref rid="B28-nutrients-09-00341" ref-type="bibr">28</xref>
]. </p>
<p>There are several additional points that warrant consideration. Firstly, several proteins from fruits and vegetables are similar to pollen allergens and may play a critical role in the pollen–fruit/vegetable cross-reactivity. For instance, some allergens in apples, pears, various stone fruits, carrots, and peanuts are homologous to the major birch pollen allergen, and can cause allergic symptoms when consumed [<xref rid="B17-nutrients-09-00341" ref-type="bibr">17</xref>
]. Therefore, children are less likely to eat them if they cause immediate symptoms. Such disease-related modification of diet may affect the observed associations between intake of certain fruits or vegetables and asthma [<xref rid="B17-nutrients-09-00341" ref-type="bibr">17</xref>
]. In one study [<xref rid="B17-nutrients-09-00341" ref-type="bibr">17</xref>
], 45% of asthmatic children had sensitization to birch pollen, and the authors reported that all negative associations between fruit and vegetable intake and asthma were no longer significant when children with food-related allergic symptoms were excluded; Secondly, it should be noted that fruit and vegetable consumption is associated with an overall healthier lifestyle. In particular, it has been reported that people with higher fruit and vegetable intakes are more likely to be non-smokers or ex-smokers [<xref rid="B83-nutrients-09-00341" ref-type="bibr">83</xref>
], or perform more physical activity [<xref rid="B84-nutrients-09-00341" ref-type="bibr">84</xref>
]. However, most of the included studies were adjusted for important lifestyle factors, such as smoking and/or physical activity status (see <xref ref-type="app" rid="app1-nutrients-09-00341">Supplementary Materials</xref>
). </p>
<p>The present systematic review has limitations that should be considered. Primarily, the criteria used for asthma diagnosis were inconsistent. Skin-prick testing and different questionnaires were used in some studies, while in other studies, asthma was diagnosed by a physician. Dietary assessment methods also varied among the studies. Some studies used a FFQ, whereas, the other studies used 7-day food records, 24 h recalls or other questionnaires. Various methods were also used to define and compare high and low intakes of fruit and vegetables (i.e., daily versus never, >3 times/week versus <3 times/week, lowest versus highest tertile of intake, >3 times/day versus <2 times/day), and thus dose-response relationships could not be assessed. Estimation of diet was also varied across the included studies, as some studies reported individual foods, while a few studies reported the dietary pattern, such as Mediterranean diet. However, only studies that reported data on fruit and vegetable intake were included. Dissimilar populations (i.e., children, adolescents, young adults and elderly) were also observed among the studies, and more than half of the studies were performed in children. The results have been presented according to study population and age, and birth cohort studies were assessed separately in the meta-analysis; however, due to the limited number of studies available for inclusion in the meta-analyses, separating the analyses for adults and children was not possible. Moreover, unmatched categories of diet exposure were observed; for example, some studies addressed the effects of total fruit and vegetable consumption [<xref rid="B26-nutrients-09-00341" ref-type="bibr">26</xref>
,<xref rid="B31-nutrients-09-00341" ref-type="bibr">31</xref>
,<xref rid="B50-nutrients-09-00341" ref-type="bibr">50</xref>
,<xref rid="B62-nutrients-09-00341" ref-type="bibr">62</xref>
], while a few studies [<xref rid="B1-nutrients-09-00341" ref-type="bibr">1</xref>
,<xref rid="B27-nutrients-09-00341" ref-type="bibr">27</xref>
,<xref rid="B43-nutrients-09-00341" ref-type="bibr">43</xref>
,<xref rid="B64-nutrients-09-00341" ref-type="bibr">64</xref>
] investigated the association between intake of a specific type of fruit and/or vegetable and asthma. Some studies also reported only total fruit intake or total vegetable intake. Therefore, only studies that reported total fruit and/or total vegetable intake were included and assessed in the meta-analysis. Moreover, some studies investigated diet as a risk factor for asthma (primary prevention), while other studies investigated diet as a disease modifier (secondary prevention). However, these different study types were assessed separately in the meta-analyses. In addition, adjustment for confounders in individual studies was performed using different covariates (see <xref ref-type="app" rid="app1-nutrients-09-00341">Supplementary Materials</xref>
). For example, gender and physical activity were adjusted in some studies, and not adjusted for in other studies. As such, it is not surprising that the protective effect of fruit and vegetables was not reported by all included studies [<xref rid="B7-nutrients-09-00341" ref-type="bibr">7</xref>
,<xref rid="B17-nutrients-09-00341" ref-type="bibr">17</xref>
,<xref rid="B24-nutrients-09-00341" ref-type="bibr">24</xref>
,<xref rid="B34-nutrients-09-00341" ref-type="bibr">34</xref>
,<xref rid="B53-nutrients-09-00341" ref-type="bibr">53</xref>
,<xref rid="B56-nutrients-09-00341" ref-type="bibr">56</xref>
]. Furthermore, one cohort [<xref rid="B48-nutrients-09-00341" ref-type="bibr">48</xref>
] and one cross-sectional study [<xref rid="B61-nutrients-09-00341" ref-type="bibr">61</xref>
] demonstrated an increased risk of asthma as vegetable or fruit consumption increased. Nonetheless, there were enough studies to see a significant protective effect of fruit and vegetables against asthma and/or wheeze using meta-analysis. Finally, we cannot rule out the possible influences of potential factors such as genetics, race and ethnicity on the association between fruit and vegetable intake and asthma. Moreover, since most of the included studies had cross-sectional design, the results could be influenced by reverse causality bias. The main strength of this systematic review is the extensive systematic literature search, clear inclusion criteria and an explicit approach to collecting data, thorough examination of the evidence, inclusion of both adults and children, inclusion of studies with various designs and meta-analysis.</p>
</sec>
<sec id="sec5-nutrients-09-00341"><title>5. Conclusions</title>
<p>In summary, overall, the findings suggest that high intakes of fruit and vegetables may have beneficial effects in asthma. However, some studies failed to attain similar results. Further studies with cohort design that differ in regards to genetic susceptibility and ethnicity/race as well as well-designed intervention trials are warranted to accurately address the effects of fruit and vegetable consumption on risk of asthma development and their role in managing asthma. More evidence is also needed from laboratory studies to identify the biological mechanisms responsible for the effects of fruit and vegetable intake on the development and management of asthma.</p>
</sec>
</body>
<back><ack><title>Acknowledgments</title>
<p>The authors would like to thank Charlotte Brew for her assistance in the study selection process.</p>
</ack>
<app-group><app id="app1-nutrients-09-00341"><title>Supplementary Materials</title>
<p>The following are available online at <uri xlink:href="http://www.mdpi.com/2072-6643/9/4/341/s1">http://www.mdpi.com/2072-6643/9/4/341/s1</uri>
.</p>
<supplementary-material content-type="local-data" id="nutrients-09-00341-s001"><media xlink:href="nutrients-09-00341-s001.docx"><caption><p>Click here for additional data file.</p>
</caption>
</media>
</supplementary-material>
</app>
</app-group>
<notes><title>Author Contributions</title>
<p>B.H., B.S.B. and L.G.W. designed the study; B.H. and B.S.B. conducted the search; B.H. analyzed the data and wrote the paper; B.S.B. and L.G.W. revised the paper; P.W. reviewed the paper; and L.G.W. had primary responsibility for the final content. All authors read and approved the final manuscript.</p>
</notes>
<notes notes-type="COI-statement"><title>Conflicts of Interest</title>
<p>The authors declare no conflict of interest.</p>
</notes>
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<floats-group><fig id="nutrients-09-00341-f001" orientation="portrait" position="float"><label>Figure 1</label>
<caption><p>Example of search strategy using PubMed for studies investigating the effects of fruit and vegetable consumption on immune responses (including immune responses to virus infection, and inflammation) and clinical outcomes in asthma.</p>
</caption>
<graphic xlink:href="nutrients-09-00341-g001"></graphic>
</fig>
<fig id="nutrients-09-00341-f002" orientation="portrait" position="float"><label>Figure 2</label>
<caption><p>Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flowchart of studies to include in systematic review of the association between fruit and vegetable intake and asthma.</p>
</caption>
<graphic xlink:href="nutrients-09-00341-g002"></graphic>
</fig>
<fig id="nutrients-09-00341-f003" orientation="portrait" position="float"><label>Figure 3</label>
<caption><p>Meta-analysis of the association between fruit intake and risk of prevalent asthma.</p>
</caption>
<graphic xlink:href="nutrients-09-00341-g003"></graphic>
</fig>
<fig id="nutrients-09-00341-f004" orientation="portrait" position="float"><label>Figure 4</label>
<caption><p>Meta-analysis of the association between fruit intake and severity of asthma.</p>
</caption>
<graphic xlink:href="nutrients-09-00341-g004"></graphic>
</fig>
<fig id="nutrients-09-00341-f005" orientation="portrait" position="float"><label>Figure 5</label>
<caption><p>Meta-analysis of the association between vegetable intake and risk of prevalent asthma.</p>
</caption>
<graphic xlink:href="nutrients-09-00341-g005"></graphic>
</fig>
<fig id="nutrients-09-00341-f006" orientation="portrait" position="float"><label>Figure 6</label>
<caption><p>Meta-analysis of the association between vegetable intake and severity of asthma.</p>
</caption>
<graphic xlink:href="nutrients-09-00341-g006"></graphic>
</fig>
<fig id="nutrients-09-00341-f007" orientation="portrait" position="float"><label>Figure 7</label>
<caption><p>Meta-analysis of the association between fruit intake and risk of prevalent wheeze.</p>
</caption>
<graphic xlink:href="nutrients-09-00341-g007"></graphic>
</fig>
<fig id="nutrients-09-00341-f008" orientation="portrait" position="float"><label>Figure 8</label>
<caption><p>Meta-analysis of the association between vegetable intake and risk of prevalent wheeze.</p>
</caption>
<graphic xlink:href="nutrients-09-00341-g008"></graphic>
</fig>
<fig id="nutrients-09-00341-f009" orientation="portrait" position="float"><label>Figure 9</label>
<caption><p>Meta-analysis of the association between fruit and vegetable intake and risk of prevalent asthma.</p>
</caption>
<graphic xlink:href="nutrients-09-00341-g009"></graphic>
</fig>
<table-wrap id="nutrients-09-00341-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">nutrients-09-00341-t001_Table 1</object-id>
<label>Table 1</label>
<caption><p>Summary of cross-sectional studies on the association between fruit and vegetable intake and asthma.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Author (Year)</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Food Measured</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Population</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Age Group (Year)</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Tool for Asthma Diagnosis</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Dietary Assessment Methods</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Variables Contrasted</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Outcomes</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cook et al. [<xref rid="B26-nutrients-09-00341" ref-type="bibr">26</xref>
], 1997</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2650</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8–11</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ <sup>a</sup>
</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">>1 time/day vs. never</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ fresh fruit, salad, green vegetables consumption: ↑ FEV1, ↔ wheeze</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">La vecchia et al. [<xref rid="B42-nutrients-09-00341" ref-type="bibr">42</xref>
], 1998</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Vegetables</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">46,693</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">≥15</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Highest (>7 serving/week) vs. lowest (<7 serving/week) tertiles</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ vegetable consumption: ↓ bronchial asthma</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Forastiere et al. [<xref rid="B43-nutrients-09-00341" ref-type="bibr">43</xref>
], 2000</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fruits </td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4104</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6–7</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire on dietary habits, citrus fruit consumption</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5–7 times/week vs. <1 time/week</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ fruit: ↓ any wheeze, ↓ shortness of breath with wheeze</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Priftanji et al. [<xref rid="B62-nutrients-09-00341" ref-type="bibr">62</xref>
], 2002</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2653</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">20–44</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire, </td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire on dietary habits</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">At least once a week</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ taking fruit and vegetables: ↓ possible allergic asthma</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Gilliland et al. [<xref rid="B50-nutrients-09-00341" ref-type="bibr">50</xref>
], 2003</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2566</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">11–19</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pulmonary function testing</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">≤lowest vs. highest intake decile</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↓ intakes of all fruit juices: ↓ FEV1 and FVC among boys, ↓ intake of vegetable: ↓ FVC in girls, ↔ other respiratory symptoms</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Woods et al. [<xref rid="B31-nutrients-09-00341" ref-type="bibr">31</xref>
], 2003</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1601</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">20–44</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ECRHS questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1–2 piece of apples, pears and berries/day and 2–4 servings leafy green vegetables and tomatoes/day</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ consumption of apples and pears: ↓ current asthma vegetable intake: ↔</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Awasthi et al. [<xref rid="B54-nutrients-09-00341" ref-type="bibr">54</xref>
], 2004</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3000</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6–7 and 13–14 </td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Validated questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F: ≥3 times/day V: ≥1 time/week</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ intakes of vegetables and fruits: ↓ wheeze</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Wong et al. [<xref rid="B63-nutrients-09-00341" ref-type="bibr">63</xref>
], 2004</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">10,902</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">10</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire, skin-prick test</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire on F & V intakes</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F: more than once daily vs. </td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ intakes of fruit and vegetables: ↓ wheeze</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Lewis et al. [<xref rid="B27-nutrients-09-00341" ref-type="bibr">27</xref>
], 2005</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fruits</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">11,562</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4–6</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">≥21 portions/week vs. 0 portions/week</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fruits: ↔ wheeze</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Nja et al. [<xref rid="B66-nutrients-09-00341" ref-type="bibr">66</xref>
], 2005</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">502</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6–16</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire, skin-prick test</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Daily intake vs. occasionally</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ intakes of fruit and vegetables: ↓ asthma</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Tabak et al. [<xref rid="B7-nutrients-09-00341" ref-type="bibr">7</xref>
], 2006</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Citrus and V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">598</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8–13</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F: Highest (287 g/day vs. lowest (79 g/day) tertiles; V: Highest (140 g/day vs. lowest (53 g/day) tertiles</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">citrus fruits, vegetables: ↔</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cardinale et al. [<xref rid="B9-nutrients-09-00341" ref-type="bibr">9</xref>
], 2007</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">130</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6–7</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Doctor-diagnosed asthma</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Always vs. never</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ intakes of fruit: ↓ asthma<break></break>
↑ intakes of salads: ↓ F<sub>E</sub>
NO</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Chatzi et al. [<xref rid="B13-nutrients-09-00341" ref-type="bibr">13</xref>
], 2007</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">690</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">7–18</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire, family history of allergic disease</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">>1 time/day vs. <1 time/day</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ intake of grapes, oranges, apples and fresh tomatoes: ↓ wheezing</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Garcia-Marcos et al. [<xref rid="B39-nutrients-09-00341" ref-type="bibr">39</xref>
], 2007</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">20,106</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6–7</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">≥3 times/week vs. never</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ intakes of fruit and vegetables: ↓ COA, ↓ CSA</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Okoko et al. [<xref rid="B1-nutrients-09-00341" ref-type="bibr">1</xref>
], 2007</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fruits</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2640</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5–10</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">>1 serving/day vs. <1 serving/month</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ intakes of apples: ↓ ever-asthma ↑ intake of bananas and apples: ↓ ever wheeze and current wheeze</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Tsai et al. [<xref rid="B61-nutrients-09-00341" ref-type="bibr">61</xref>
], 2007</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2218</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">11–12</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ATS questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Daily intake vs. never</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ Fruit intakes: ↓ wheezing without cold, ↓ asthma, ↑ vegetable consumption: ↑ asthma</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Barros et al. [<xref rid="B67-nutrients-09-00341" ref-type="bibr">67</xref>
], 2008</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">174</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">>16</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Doctor-diagnosed asthma and questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F: <178.4 g/day vs. >304.97 g/day; V: <211.54 g/day vs. >426.63 g/day</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ consumption of fresh fruit: ↓ non-controlled asthma; vegetable intake: ↔; F&V: ↔ exhaled NO</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Castro-Rodriguez et al. [<xref rid="B40-nutrients-09-00341" ref-type="bibr">40</xref>
], 2008</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1784</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4.08</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">>3 times/week vs. never</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ intake of vegetable: ↓ wheezing; fruits intake: ↔</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Garcia et al. [<xref rid="B64-nutrients-09-00341" ref-type="bibr">64</xref>
], 2008</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fruits</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3256 children and 3829 adolescents</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6–7 and 13–14</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire on dietary habits</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">≥3 times/week vs. occasionally</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ fruit consumption: ↓ current asthma symptoms among the 13–14 year age-group</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Takaoka et al. [<xref rid="B57-nutrients-09-00341" ref-type="bibr">57</xref>
], 2008</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">153 females</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Mean 21</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Doctor -diagnosed asthma, ISSAC/ECRHS questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">almost daily vs. never</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ intake of fruit: ↓ wheeze<break></break>
vegetables: ↔</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Nagel et al. [<xref rid="B70-nutrients-09-00341" ref-type="bibr">70</xref>
], 2010</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">50,004 <sup>b</sup>
</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8–12</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">≥3 times/week vs. never/occasionally</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ consumption of green vegetables: ↓ wheezers in non-affluent countries only; ↑ fruit intake: ↓ prevalence of current wheeze in affluent and non-affluent countries</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Arvaniti et al. [<xref rid="B34-nutrients-09-00341" ref-type="bibr">34</xref>
], 2011</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">700</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">10–12</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">At least once/day</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fruits and vegetables: ↔ asthma</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Lawson et al. [<xref rid="B51-nutrients-09-00341" ref-type="bibr">51</xref>
], 2011</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4726</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">11–15</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Doctor-diagnosed asthma</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Validated questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">High vs. low consumption</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ vegetable consumption: ↓ current asthma; fruit intake: ↔</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Rosenlund et al. [<xref rid="B17-nutrients-09-00341" ref-type="bibr">17</xref>
], 2011</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2447</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Doctor-diagnosed asthma</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Quartile 4 (7.1 serving/day) vs. quartile 1 (1.8 serving/day)</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fruits and vegetables: ↔; apples/pears, carrots: ↓ asthma</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Rosenkranz et al. [<xref rid="B32-nutrients-09-00341" ref-type="bibr">32</xref>
], 2012</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">156,035</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">≥45</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire, self-reported information</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Quintile 5 vs. 1</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ fruit and vegetable intake: ↓ asthma in men </td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Agrawal et al. [<xref rid="B55-nutrients-09-00341" ref-type="bibr">55</xref>
], 2013</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">156,316</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">20–49</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Daily intake vs. occasionally/never</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ fruit and vegetable intake: ↓ asthma</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ng et al. [<xref rid="B69-nutrients-09-00341" ref-type="bibr">69</xref>
], 2013</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2478</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">≥55</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Spirometry</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SQFFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Once/day</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fruits and vegetables: ↔ respiratory function</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Alphantonogeorgos et al. [<xref rid="B35-nutrients-09-00341" ref-type="bibr">35</xref>
], 2014</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1125</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">10–12</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">KIDMED FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Once/day</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ intake of one fruit or fruit juice and vegetable: ↓ ever wheezing and current wheezing</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Papadopoulou et al. [<xref rid="B36-nutrients-09-00341" ref-type="bibr">36</xref>
], 2014</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2023</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">9–10</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Doctor-diagnosed asthma</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SQFFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Daily vs. never</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fruits, vegetables: ↔ asthma</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Gomes de Luna Mde et al. [<xref rid="B46-nutrients-09-00341" ref-type="bibr">46</xref>
], 2015</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3015</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">13–14</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">≥3 times/week vs. < times/week</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ Fruit intake: ↓ asthma; vegetable intakes: ↔</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p><sup>a</sup>
Abbreviation: BMI, body mass index; COA, current occasional asthma; CSA, current severe asthma; ECRHS, the European community respiratory health survey screening questionnaire; F<sub>E</sub>
NO, fractional exhaled nitric oxide; FFQ, food frequency questionnaire, F & V, fruits and vegetables; SQFFQ, semi-quantitative food frequency questionnaire; ISAAC, international study of asthma and allergies in childhood questionnaire; <sup>b</sup>
29 centres in 20 countries (ISAAC Phase II).</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="nutrients-09-00341-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">nutrients-09-00341-t002_Table 2</object-id>
<label>Table 2</label>
<caption><p>Summary of case-control studies on the association between fruit and vegetable intake and asthma.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Author (Year)</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Food Measured</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Population</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Age (Year)</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Tool for Asthma Diagnosis</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Dietary Assessment Methods</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Variables Contrasted</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Outcomes</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Hijazi et al. [<xref rid="B68-nutrients-09-00341" ref-type="bibr">68</xref>
], 2000</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V <sup>a</sup>
</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">114 cases with a history of asthma and wheeze in the last 12 months and 202 controls</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">12</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire and skin test</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SQFFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">>3 time/day vs. <2</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↓ vegetables intake: ↑ asthma; fruit intake ↔</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Shaheen et al. [<xref rid="B18-nutrients-09-00341" ref-type="bibr">18</xref>
], 2001</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">607 cases and 864 controls</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">16–50</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">≥5 times/week vs. </td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↓ Total fruit and total vegetable consumption: ↑ asthma </td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Patel et al. [<xref rid="B23-nutrients-09-00341" ref-type="bibr">23</xref>
], 2006</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">515 cases and 515 controls</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">45–75</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Physician diagnosed asthma</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">7-day food diaries</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Consumption above the median (F: 132.1 g, V: 96.9 g vs. no consumption)</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ intake of citrus fruit and total fruit intakes: ↓ asthma; vegetable intake ↔</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pastorino et al. [<xref rid="B44-nutrients-09-00341" ref-type="bibr">44</xref>
], 2006</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">528</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">13–14</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire about dietary habits</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Weekly or daily vs. never consumption</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ intake of cooked vegetables: ↓ asthma; fruit intake ↔</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Romieu et al. [<xref rid="B19-nutrients-09-00341" ref-type="bibr">19</xref>
], 2009</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">158 cases and 50 controls followed for 22 weeks</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6–14</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Physician diagnosed asthma</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V index = 0 vs. F & V index =4 </td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ FVI: ↑ FEV1 and FVC; ↓ IL-8 in nasal lavage, ↓ FeNO level</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Mendes et al. [<xref rid="B45-nutrients-09-00341" ref-type="bibr">45</xref>
], 2011</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">104 cases with persistent asthma and 67 controls with intermittent asthma</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2–12</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Dietary data collected during the last 30 days</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Regular vs. occasional consumption</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ consumption of fruits: ↓ persistent asthma</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Protudjer et al. [<xref rid="B20-nutrients-09-00341" ref-type="bibr">20</xref>
], 2012</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">149 cases and 327 controls from a Cohort study</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8–10 and 11–14</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Skin-prick test ≥3 mm and asthma symptoms</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">High vs. low score (>6 times/day vs. Almost never)</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ vegetable intake: ↓ allergic asthma, ↓ moderate/severe AHR; fruit intake: ↔</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Han et al. [<xref rid="B49-nutrients-09-00341" ref-type="bibr">49</xref>
], 2015</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">351 cases and 327 controls</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6–14</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Physician-diagnosed asthma and ≥1 episode of wheeze in the previous year</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Quartile 4 vs. quartile 1</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ consumption of vegetables: ↓ asthma, ↓ serum IL-17F</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p><sup>a</sup>
Abbreviation: BMI, body mass index; FFQ, food frequency questionnaire, F & V, fruits and vegetables; ISAAC, international study of asthma and allergies in childhood questionnaire; MDS, Mediterranean diet score; SQFFQ, semi-quantitative food frequency questionnaire.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="nutrients-09-00341-t003" orientation="portrait" position="float"><object-id pub-id-type="pii">nutrients-09-00341-t003_Table 3</object-id>
<label>Table 3</label>
<caption><p>Summary of cohort studies on the association between fruit and vegetable intake and asthma.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Author (Year)</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Food Measured</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Population</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Age Group (Year)</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Follow-Up (Year)</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Tool for Asthma Diagnosis</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Dietary Assessment Methods</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Variables Contrasted</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Outcomes</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Butland et al. [<xref rid="B22-nutrients-09-00341" ref-type="bibr">22</xref>
], 1999</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fresh fruit</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">11,352</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0–33 </td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">33</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Wheezing/whistling in the chest in the past doctor diagnosis</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Validated questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">>1 time/day vs. never</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ Fresh fruit, salads or raw vegetables consumption: ↓ the frequent wheezing</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Knekt et al. [<xref rid="B52-nutrients-09-00341" ref-type="bibr">52</xref>
], 2002</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Orange, apple, grapefruit, onion, white cabbage, berries, juices</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">382</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">30–69</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">20</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Dietary history</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Quartile 4 vs. 1</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ apple and orange intakes: ↓ asthma</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Farchi et al. [<xref rid="B41-nutrients-09-00341" ref-type="bibr">41</xref>
], 2003</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Cooked vegetables, salads, tomatoes, fresh fruit, citrus fruit, kiwi</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4104</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6–7</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">>4 times per week vs. never</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ Consumption of tomatoes, fruits and citrus fruit: ↓ shortness of breath</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Romieu et al. [<xref rid="B58-nutrients-09-00341" ref-type="bibr">58</xref>
], 2006</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">68,535 women</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">40–65</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Quartile 4 vs. Quartile 1 (fruits: >336 vs. ≤145.3 g/day and vegetables: >90 vs. ≤39.3 g/day)</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ Consumption of tomatoes, carrots, and leafy vegetables: ↓ asthma</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fitzsimon et al. [<xref rid="B65-nutrients-09-00341" ref-type="bibr">65</xref>
], 2007</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">631 mother-child pair</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Doctor-diagnosed asthma</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SQFFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Quartile 4 (8.9 serving/day) vs. quartile 1(2.3 serving/day)</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ Quartile of F & V intake in pregnancy: ↓ asthma in children</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Willers et al. [<xref rid="B21-nutrients-09-00341" ref-type="bibr">21</xref>
], 2007</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1212 mother-child pair</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">At birth</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">>4 times/week vs. 0 ↔ 1 time/week</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ Maternal apple intake: ↓ ever wheeze, ↓ ever asthma and doctor-confirmed asthma<break></break>
vegetables: ↔</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Chatzi et al. [<xref rid="B37-nutrients-09-00341" ref-type="bibr">37</xref>
], 2008</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">507 mothers and 468 children</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6.5</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6.5</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire on wheeze, whistling and skin-prick test</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Daily or weekly consumption vs. never</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ Consumption of vegetables: ↓ persistent wheeze, fruits: ↔</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Willers et al. [<xref rid="B47-nutrients-09-00341" ref-type="bibr">47</xref>
], 2008</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2832 mother-child pairs</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3 month–8 year</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire about both mother’s and child’s diet</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Daily vs. rare intake</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ Fruit intake: ↓ wheeze vegetables: ↔; F & V intake: ↔</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Bacopoulou et al. [<xref rid="B33-nutrients-09-00341" ref-type="bibr">33</xref>
], 2009</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2133 children</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">From birth</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">18</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Doctor-diagnosed asthma and questionnaire about detailed information on asthma</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Validated questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Daily intake vs. never</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ Fruit and vegetable intake: ↓ current asthma at 18 years </td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Miyake et al. [<xref rid="B56-nutrients-09-00341" ref-type="bibr">56</xref>
], 2010</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">763 mother-child pair</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">16–24 month</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">DHQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F: Quartile 4 (290.8 g/day) vs. 1 (49.6 g/day) V: Quartile 4 (288.4 g/day) vs. 1 (90.9 g/day)</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V intake: ↔ wheeze</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Uddenfeldt et al. [<xref rid="B59-nutrients-09-00341" ref-type="bibr">59</xref>
], 2010</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fruit</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8066 females and males</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">16, 30–39, 60–69 </td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">13</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire about frequency of current consumption</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Daily intake vs. never</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ Fruit intake: ↓ asthma incidence </td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Nwaru et al. [<xref rid="B53-nutrients-09-00341" ref-type="bibr">53</xref>
], 2011</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Food-based antioxidants</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2441 mother-child pair</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FFQ</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Quantity of intake in diet</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Food-based antioxidants: ↔ asthma</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Willers et al. [<xref rid="B48-nutrients-09-00341" ref-type="bibr">48</xref>
], 2011</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F & V</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4146 children</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2–3 and 7–8 </td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ISAAC questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Annual FFQ </td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Once weekly vs. long-term intake from age 2–8 years</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↑ Fruit intake: ↓ asthma symptoms; cooked ↑ vegetables intake: ↑ asthma</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p><sup>a</sup>
Abbreviation: BMI, body mass index; DHQ, dietary habit questionnaire; FFQ, food frequency questionnaire, F & V, fruits and vegetables; ISAAC, international study of asthma and allergies in childhood questionnaire, SQFFQ, semi quantitative food frequency questionnaire.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="nutrients-09-00341-t004" orientation="portrait" position="float"><object-id pub-id-type="pii">nutrients-09-00341-t004_Table 4</object-id>
<label>Table 4</label>
<caption><p>Summary of experimental studies on the association between fruit and vegetable intakes and asthma.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Author (Year)</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Study Population</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Age Group (Year)</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Notes</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Intervention</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Duration of Treatment</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Tool for Asthma Diagnosis</th>
<th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Outcomes</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Wood et al. [<xref rid="B28-nutrients-09-00341" ref-type="bibr">28</xref>
], 2008</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">32 adults</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Mean age of 52.1</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Participants were on the low antioxidant diet for 10 days before the study commenced.</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Tomato extract (45 mg lycopene/day) vs. tomato juice (45 mg lycopene/day) vs. placebo</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3 × 7 day with a 10 days wash-out period between each treatment</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Doctor-diagnosed asthma and having current (past 12 months) episodic respiratory symptoms</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The LAO diet: ↓ %FEV1 <sup>a</sup>
and %FVC, ↑ neutrophils increased both tomato juice and extract: ↓ airway neutrophil influx Neutrophils tomato extract: ↓ sputum neutrophil elastase activity</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Baines et al. [<xref rid="B29-nutrients-09-00341" ref-type="bibr">29</xref>
], 2009</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">10 adults diagnosed with stable asthma</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Mean age of 63</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">No control group</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The LAO diet <sup>b</sup>
</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">14 days</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Doctor-diagnosed asthma and respiratory symptoms</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The LAO diet: ↑ genes involved in the inflammatory and immune responses including the innate immune receptors TLR2, IL1R2, CD93, ANTXR2, the innate immune signalling molecules IRAK2, 3, MAP3K8 and neutrophil proteases.</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Fogarty et al. [<xref rid="B24-nutrients-09-00341" ref-type="bibr">24</xref>
], 2009</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Intervention group n = 3233, Placebo group n = 3506</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4–6</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The control group received usual diet.</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">A daily piece of fruit (generally including apples, oranges or pears) adding to their usual diet</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1 year</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Questionnaire</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↔</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Wood et al. [<xref rid="B30-nutrients-09-00341" ref-type="bibr">30</xref>
], 2012</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">137 adults</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Mean age of 56</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Participants randomized to the low vs. high antioxidant diet (5 servings of vegetables and 2 servings of fruit daily) for 14 days before the study commenced.</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">High antioxidant diet group received placebo, while, low antioxidant diet group received tomato extract (45 mg lycopene/day).</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">14 weeks</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Doctor-diagnosed asthma and having current (past 12 months) episodic respiratory symptoms</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The LAO diet: ↑ exacerbation, ↓ %FEV1 and %FVC</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Lee et al. [<xref rid="B60-nutrients-09-00341" ref-type="bibr">60</xref>
], 2013</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">192</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">10–12</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The control group received placebos</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">“fruit and vegetable” capsule <sup>c</sup>
+ Fish oil capsules+ Probiotic capsules vs. placebo</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">16 weeks</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Doctor-diagnosed asthma</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">The supplement group: ↑ FEV1, FVC and FEV1:FVC ratio, ↓ proportion of children using ICS </td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Garcia-Larsen et al. [<xref rid="B25-nutrients-09-00341" ref-type="bibr">25</xref>
], 2014</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">32</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6–10</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Participants were randomly allocated to one of four groups. The control group received usual diet.</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Having an apple or a banana or an apple + banana in addition to their normal diet</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1 month</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Respiratory tests</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Groups 2 (adding banana) and 3 (adding banana + apple): ↓ levels of F<sub>E</sub>
NO</td>
</tr>
<tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Calatayud-Saez et al. [<xref rid="B38-nutrients-09-00341" ref-type="bibr">38</xref>
], 2016</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">104 children with childhood asthma criteria for at least 1 year</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1–5</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">No control group</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Dietary re-education by a nutritional education programme named “Learning to Eat from the Mediterranean”</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">1 year</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Doctor-diagnosed asthma</td>
<td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">↓ The use of ICS</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p><sup>a</sup>
Abbreviation: F<sub>E</sub>
NO, fractional exhaled nitric oxide; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; ICS, inhaled corticosteroids; LAO, low antioxidant diet; <sup>b</sup>
Included no more than one piece of fruit and two serves of vegetables per day and avoidance of tea, coffee, red wine, fruit juices, nuts, seeds, vitamin or mineral supplements and aspirin; <sup>c</sup>
Contains 400 mg concentrate derived from grapes, plums, blueberries, raspberries, cranberries, cherries, cowberries, strawberries, artichokes, beets, carrots, broccoli, white cauliflower, kale, celery, and spinach.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
</record>
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