Diet and asthma: need to account for asthma type and level of prevention

KEYWORDS:

• Dietary intake
• asthma incidence
• asthma control
• epidemiology
• primary prevention
• secondary prevention
• asthma heterogeneity

Asthma is affecting around 300 million individuals worldwide [1]. The prevalence of asthma has markedly increased over the past decades, especially in Westernized countries [2]. Aside from genetic determinants, many experts have proposed that these increases may be a consequence of changing environmental and/or lifestyle factors [2]. For example, the modification of dietary habits, the decrease in physical activity, and the obesity epidemic have been suggested to play a role in the increase of asthma [2]. Several hypotheses and mechanisms have been raised to explain the role of diet in asthma, including oxidative stress and inflammation, and more recently, vitamin D, epigenetic regulation, and imbalance in the gut microbiome. Asthma is a chronic inflammatory disease of the airways, and endogenous reactive oxygen species have been implicated in its pathogenesis. Different antioxidants from diet (vitamins A, E, C) may have different mechanisms through which they might protect lung tissue against oxidative damage [3]. It has been hypothesized that the increased intake of proinflammatory omega-6 polyunsaturated fatty acids (PUFAs) and the decreased intake of omega-3 PUFAs in Western countries, have strongly contributed to the rise in asthma prevalence [4]. More recently, several mechanisms by which vitamin D may affect asthma have emerged, including (1) vitamin D effects on airway smooth muscle modulation of gene expression and chemokine secretion, leading to decreased alveolar smooth muscle proliferation and decreased airway inflammation, two effects that might prevent or improve airway obstruction; (2) vitamin D-mediated reversal of steroid resistance; and (3) improved handling of respiratory infections, leading to decreased asthma exacerbation [5]. It has also been proposed that changes in DNA methylation can affect the pathogenesis of asthma by increasing or decreasing the expression of disease-susceptibility genes, and methyl donors for DNA methylation are mostly derived from dietary methyl groups (folate, vitamin B12, and choline) [3]. In addition, a growing number of investigators hypothesize that an imbalance in the gut microbiome caused by changes in the diet over the past decades may cause dysfunction of the immune system, leading to the development of asthma and allergy [6]. In children, the specific gut microbiota accompanied by a reduction of short-chain fatty acids (SCFAs) was associated with a higher risk of incident asthma [7], and results from a recent study showed that fiber intake altered the composition of both the gut, and to a lesser degree the lung, microbiota [8]. Higher levels of SCFAs, produced by bacteria in the gut during fermentation of insoluble fiber from dietary plant manner, were recently associated with a healthy diet as defined by a high intake of fruit, vegetables, and legumes (e.g. high content fiber foods) [9]. In this line, primary prevention by using probiotic might be relevant even if the level of evidence is still limited [10].

Over the last 20 years, the role of diet in asthma has gained interest in the international literature, and a substantial number of papers have been published on this topic [11]. Taken together, the literature is inconclusive, probably due to the complexity of both the exposure and outcome and, consequently, of their association. Indeed, published papers are very heterogeneous regarding diet assessment (food frequency questionnaire/24-hour recall/biomarkers), diet estimation (nutrients/foods/dietary patterns), and window of exposure (antenatal/childhood/adulthood diet); they also differ regarding the description of asthma (heterogeneity/phenotype/endotype), but also regarding the level of prevention studied (primary/secondary). These final points are the focus of this editorial and, in our opinion, is a distinction that is too often lost in the literature. In short, we believe that there are not enough papers addressing the issue of asthma type in relation with diet, and too much mixing of results from studies that investigated diet as a risk factor for the onset of the disease (epidemiologic studies of general population) versus diet as a disease modifier (epidemiological and interventional studies among individuals with asthma).

1. Diet: a complex variable in nutritional epidemiology

Diet is not a single exposure, but rather a complex set of many intercorrelated continuous variables. Therefore, several tools have been developed to collect data on diet, each with their strengths and limitations. The three most common methods used are the 24-hour dietary recall, the diet record, and the food-frequency questionnaire [12].

Regarding estimation of diet, studies on specific foods or nutrients have traditionally been conducted. However, several conceptual and methodological limitations have been raised [13], mostly because we do not consume isolated foods or nutrients, but rather meals consisting of a complex combination of foods, which themselves contain nutrients, which can interact with each other. Therefore, studying dietary patterns has been proposed to estimate the effects of overall diet, rather than the effects of specific foods or nutrients. Two general approaches have been used to define dietary patterns in observational studies [13]. The first approach, called a priori, is based on prevailing hypotheses and guidance about the role of nutrients in disease prevention, whereas the second approach, called a posteriori is data driven. Studying dietary patterns is particularly relevant when investigating the role of diet on diseases such as asthma, for which no specific food or nutrient has clearly been identified.

Last, dietary habits evolve throughout life and may thus influence health in different ways and by different mechanisms, according to the window of exposure. Under the theory of Developmental Origins of Health and Disease, the importance of maternal diet during pregnancy on child health is now largely recognized [14]. Whereas maternal diet during pregnancy may have long-term effects on the offspring development and health, dietary habits during childhood and through adult life, may also have shorter-term effects.

2. Asthma heterogeneity

Asthma is a complex disease, with phenotypic variability. Its clinical expression varies over time, on different time scales: by day, by month, according to seasons, but also over the course of several years; asthmatic patients may experience periods of remission, sometimes followed by a relapse of symptoms. Asthma can occur at any age, but usually begins during early childhood. Asthma incidence during childhood is greater in boys than in girls whereas after puberty, asthma incidence is greater in women than in men, and remains higher throughout the reproductive years. Asthma in the elderly is characterized by more frequent irreversible airway obstruction and accelerated lung function decline, due to airway remodeling (causing airway wall thickening), and potential overlap with chronic obstructive pulmonary disease (COPD), the so-called asthma-COPD overlap syndrome (ACOS) [15]. Recent studies have increasingly focused on this remarkable heterogeneity, and there is growing acceptance that asthma involves multiple phenotypes or consistent groupings of characteristics [16].

Besides the clinical approach, epidemiological research performed over the past one to two decades has sought to better understand the heterogeneous clinical nature of asthma using non-biased analyses in which there are no preconceived assumptions about the relationships among asthma features [17]. Novel phenotypes have been identified using such comprehensive statistical-based approaches able to simultaneously integrate multiple disease features, including age at onset, atopy, severity of airways obstruction and requirement for medication [17]. Examples of these phenotypes include early-onset mild allergic asthma, later-onset asthma associated with obesity, and severe non-atopic asthma with frequent exacerbations [17]. More recently, it has been proposed that the concept of phenotype should be further evolved to that of the ‘endotype,’ i.e. a subtype of a condition which is defined by a distinct functional or pathophysiological mechanism [18]. Obesity-related asthma is increasingly recognized as distinct from early-onset allergic asthma, with former having a later age of onset, a more severe course, the presence of neutrophils and an IL-17 signature [19]. Anti/proinflammatory dietary intakes may be particularly relevant for obesity-related asthma. Another endotype that might be relevant for fiber and/or SCFA intakes is the allergic bronchopulmonary mycosis (ABPM) endotype, which is characterized by a hypersensitivity reaction to the colonization of the airways by molds, most frequently Aspergillus fumigatus [18].

In the context of this heterogeneity, is it not reasonable to posit that the role of diet might differ across these different asthma phenotypes?

3. Diet and asthma: primary prevention

As defined by the World Health Organization (WHO), primary prevention is directed toward preventing the initial occurrence of a disorder [20]. Overall, few studies have been performed on primary prevention of asthma with diet, and all of them have considered asthma as a binary (yes/no) outcome (wheezing in early childhood, childhood-onset asthma, or adult-onset asthma) [11].

Regarding maternal diet during pregnancy, a small number of cohort studies have highlighted associations between wheezing in the first years of life and reduced maternal intake of vitamins E and D, zinc, and omega-3 PUFAs during pregnancy [11,21]. The few longitudinal studies conducted on associations between maternal dietary patterns during pregnancy and wheeze/asthma in the offspring reported, overall, no association [21]. Regarding diet during childhood, few longitudinal studies have been published. The association between diet and childhood asthma is moderate, at best, with observational studies reporting ‘protective’ associations for fruits and vegetables, and fish intake [11,22]. To our knowledge, only one longitudinal study on dietary patterns and asthma has been published and reported a small positive association between adherence to a Western diet and incident wheezing in children [23]. Regarding diet during adulthood, the few longitudinal studies show, overall, no association [11].

4. Diet and asthma: secondary prevention

As defined by the WHO, secondary prevention seeks to arrest or retard existing disease and its effects through early detection and appropriate treatment; or to reduce the occurrence of relapses and the establishment of chronic conditions through, for example, effective rehabilitation [20]. In this line, the last Global Initiative for Asthma Guidelines encourages patients with asthma to consume a diet high in fruit and vegetables for its general health benefits [24]. But up to now, the role of diet as a disease modifier (e.g. on asthma control, frequency of asthma attacks, exacerbations of asthma, lung function decline, bronchial hyperresponsiveness, quality of life) remains underexplored.

Regarding diet during childhood, only few studies have been published, all on vitamin D either with asthma control, severity, or exacerbations [25]. Overall, they reported that higher serum levels of 25(OH)D are associated with a reduced risk of asthma exacerbations [25]. Regarding diet in adulthood, we reported among women with asthma from a large French cohort study, that frequent asthma attacks were more common among those with a ‘Western’ dietary pattern and less common among those with a ‘nuts and wine’ pattern [26]. Likewise, one case–control study in Portugal showed that a higher ‘alternate Mediterranean Diet’ score was associated with better asthma control [27]. An RCT conducted in New Zealand reported no improvement in asthma control over 12 weeks for the interventional groups encouraged to adopt a Mediterranean diet, but perhaps due to the small sample size and the short follow-up time [28]. Recently, a pilot RCT performed in the USA reported that adults with persistent asthma had better asthma control after a 6 months of healthy eating intervention based on the Dietary Approaches to Stop Hypertension score [29].

5. Conclusion

Even if dietary intake appears to have little (if any) role as a cause of ‘asthma’ (single disease), the role of diet in the etiology of specific asthma phenotypes is largely unknown. Regarding secondary prevention, the role of diet as a disease modifier has more promise, but again, we encourage studies with a careful consideration for period of dietary intakes (during pregnancy, early life/infancy, or adulthood) and better asthma phenotyping to be able to really understand how diet might affect the evolution and the heterogeneity of asthma. A clearer understanding of the likely differences in the diet-asthma association – by asthma type and by level of prevention – will guide future research and, ultimately, provide the required evidence to define the role of dietary interventions in clinical guidelines.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.