2017 March
Banafshe Hosseini | Bronwyn S. Berthon | Peter Wark | and Lisa G. Wood
Abstract
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 (n = 58). Studies used cross-sectional (n = 30), cohort (n = 13), case-control (n = 8) and experimental (n = 7) designs. Most of the studies (n = 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 (n = 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 (p < 0.05). Likewise, vegetable intake was negatively associated with risk of prevalent asthma (p < 0.05). Seven studies examined immune responses in relation to fruit and vegetable intake in asthma, with n = 6 showing a protective effect against either systemic or airway inflammation. Fruit and vegetable consumption appears to be protective against asthma.
1. Introduction
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 [1].
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 [2].
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 [3].
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 [4,5].
The considerable morbidity related to asthma may be ameliorated by addressing modifiable risk factors such as diet [6]. 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 [7]. 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 [8,9].
Oxidative stress plays a major role in the pathophysiology of asthma, due to chronic activation of airway inflammatory cells [10]. 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 [11,12].
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 [8]. Fresh fruit and vegetables provide rich sources of antioxidants and other biologically active substances (such as flavonoids, isoflavonoids and polyphenolic compounds) [12].
Studies have shown that diets with low average consumption of fruit and vegetables play a major role in the development of allergic diseases [1,7], and may augment oxidative stress in asthma [13]. 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 [7].
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 [8].
Currently available asthma medications, such as glucocorticoids, are ineffective in some cases such as viral-induced exacerbations [14]; and prolonged treatment with these therapeutic agents can result in adverse effects, such as pneumonia, cataracts, and osteoporosis [15]. 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.
2. Methods
2.1. Search Strategy
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 Figure 1 for an example of the search strategy.
2.2. Study Selection
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.
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.
2.3. Study Quality
Eligible studies were assessed in terms of the methodological quality based on a standardised critical appraisal checklist designed by the American Dietetic Association [16]. 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.
2.4. Data Extraction and Study Synthesis
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.
2.5. Statistical Methods
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 I2 > 50 and p < 0.1. Meta-analysis was performed using random effect modelling if I2 > 50 and fixed effect modelling was used if I2 < 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. [17], while other studies used an FFQ which included over 50 items, such as Shaheen et al. [18] (>200 items), Romieu et al. [19] (108 items), and Protudjer et al. [20] (72 items).
In addition, some of the FFQs were modified for use in children [21]. 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). Table 1, Table 2 and Table 3 show how the variables are contrasted in different studies.
