Novel dietary risk factors for asthma

KEYWORDS:

• Processed meat
• Western diet
• sugar sweetened beverages
• asthma incidence
• asthma symptoms
• adults
• epidemiology

Asthma is a chronic inflammatory disease of the airways, affecting >270 million individuals worldwide [1]. The prevalence of asthma has markedly increased over the last decades, especially in Westernized countries [1,2]. The causes of this increase are unclear but cannot be attributed only to changes in diagnosis or better reporting of symptoms over time [2]. This increase may be a consequence of changing environmental and lifestyle factors during societal urbanization – e.g., modification of dietary habits, with decreased consumption of fresh fruits and vegetables, and increased access to prepackaged ‘convenience’ foods (such as processed refined foods and saturated fats and carbohydrate sweeteners, all of which contribute to obesity) [3]. 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 [3,4]. To date, most diet–lung research has focused on favorable dietary factors with antioxidant or anti-inflammatory properties, such as fruits and vegetables, and to a lesser extent on the Prudent or Mediterranean diet [3,4]. Although obesity is a major risk factor for asthma – and diets that produce obesity are typically high in red and processed meats, in fats and fried foods, and in sugar – little attention has been paid to the impact of unfavorable dietary factors on adult asthma [5]. This idea is the focus of our editorial.

1. The Western diet

Diet is not a single exposure, but rather a complex set of many intercorrelated continuous variables [6]. Dietary studies traditionally estimate intake of specific foods or nutrients. However, several conceptual and methodological limitations have been raised, mostly because we do not consume isolated foods or nutrients, but rather meals. Therefore, studying dietary patterns has been proposed to better estimate the effects of overall diet [6]. Using a data-driven approach to derive dietary patterns, with dietary exposure summarized using exploratory methods (e.g., principal component analysis [PCA] or cluster analysis), two main dietary patterns are typically identified: a ‘Prudent’ dietary pattern characterized by a high intake of fruit, vegetables, lean meat, fish and wholegrain cereals, and a ‘Western’ dietary pattern characterized by a high intake of processed refined foods, and foods high in sugars and fats [6]. To our knowledge, about 15 studies worldwide have looked at the association between dietary patterns, mostly derived using PCA, with asthma symptoms or incidence in adults, and they have yielded mixed findings [7–10].

PCA is frequently criticized for being a descriptive method of data reduction [6]. A potentially better approach is structural equation modeling, which allows the testing of a statistical model specifying dietary patterns as latent variables. These methods include, among others, confirmatory factor analysis (CFA) which is the structural equation modeling equivalents of PCA. Interestingly, when we compared the alternative use of CFA to PCA for the identification of dietary patterns, we reported a positive association between the Western diet and adult-onset asthma only when CFA was used [8]. Another limitation is that results from dietary patterns derived with the use of PCA have not always been reproducible across different settings [10]. To address this, Bakolis et al. used a novel approach for the analysis of food frequency questionnaire data across countries, a meta‐analytic approach to PCA. In nine European populations participating in the Global Asthma and Allergy Network of Excellence (GA2LEN), they reported an increase in asthma symptoms in those eating a diet rich in animal proteins and carbohydrates, as reflected by the Western diet [10].

Although there is substantial heterogeneity among studies in methodology (PCA vs. other techniques for the grouping of variables), study design (e.g., sample size, geographic region), and asthma outcomes (incidence, symptoms or prevalence), we believe that the Western dietary pattern is associated with asthma-related outcomes in adulthood. Intake of processed refined foods, as reflected by the Western diet, lacks vitamins and micronutrients essential in the growth, development, and functioning of both immunological and respiratory system and that the mentioned dietary factors can significantly influence gut microbiome [3]. Urbanization is also characterized by a decrease of physical activity and a higher amount of time spent indoors. Since vitamin D is obtained mostly by dermal synthesis through exposure to UVB light, rather than from dietary intake, vitamin D deficiency is a common feature of a Western diet, and is a likely risk factor of asthma exacerbations [11]. Interestingly, using a priori dietary scores reflecting a better adherence to a healthy diet, several studies have reported a decreased risk of asthma symptoms [12,13]. Although these studies could indirectly estimate the effects of the absence of these healthy foods in a Western diet, we believe it would be helpful to create dietary scores that reflect the unhealthy Western diet.

2. Processed meat consumption

Processed meat is an important component of the Western diet. Recently, the World Health Organization (WHO) classified processed meat as carcinogenic to humans [14]. High-processed meat consumption has also been associated with increased risk of all-cause mortality and is a risk factor for several major chronic diseases, such as type 2 diabetes, coronary heart disease, and stroke [15].

The exact role of processed meat in the pathogenesis of asthma remains unclear and mechanistic studies are lacking, but one possible mechanism is the nitrites added to meat products [16,17]. The sodium salts of nitrate (NaNO3) and nitrite (NaNO2) are used in the curing and preserving of processed meat. Based on the processing technology, processed meat products that are treated with small amounts of nitrite, either as dry salt or as salt solution in water, are classified as ‘cured’ meat [16,17]. Regulations controlling the use and level of curing agents are country-specific. Nitrites are used for three purposes: to preserve color, especially the pink color for hot dogs and other cured meats; to enhance flavor by inhibiting rancidity; and to protect against bacterial growth. Nitrites are rapidly absorbed both in the small intestine and in the stomach, where they may react with secondary or tertiary amines and amides to reactive nitrogen species (RNS), such as N-nitroso compounds. With regard to the lung, the reactive oxygen species (ROS) and RNS can amplify inflammatory processes in the airways and lung parenchyma causing lipid peroxidation, DNA damage, inhibition of mitochondrial respiration, and inactivation of proteins. The long-term persistence of nitrosative stress and of inflammation may contribute to progressive deterioration of pulmonary function and asthma pathogenesis [16,17].

Processed meat intake has been associated with increased risk of lung cancer, decline in lung function and COPD [18,19]. To date, four studies have examined the association between processed meat intake and asthma-related outcomes, either with cross-sectional or longitudinal designs, and in different countries [16,19–21]. More than 10 years ago, we reported the longitudinal association between processed meat intake and the risk of asthma in US studies of health professionals [19,20]. Using doctor-diagnosed asthma, which rather considered asthma as a dichotomous trait rather than a complex disease with clinical phenotypic heterogeneity and temporal phenotypic variability, we observed no significant association (whereas we reported within the same studies, a strong positive association with the risk of newly-diagnosed COPD) [19,20]. More recently, using the asthma symptom score as a continuous definition of asthma, we reported both in longitudinal [16] and cross-sectional [21] studies in France, a positive association between high-processed meat intake and worsening asthma symptoms, independent of obesity. The asthma symptom score, proposed as a continuous measure of asthma, was particularly helpful for identifying risk factors in epidemiological studies [22].

In our opinion, processed meat intake appears to be an important target for primary prevention of adult asthma. We encourage additional research with better asthma phenotyping and in different countries to better understand how processed meat intake affects onset of respiratory symptoms.

3. Sugar-sweetened beverages consumption

Another important component of the Western diet is sugar-sweetened beverages (SSB). Research has shown that SSB are one of the major determinants of obesity and diabetes [23]. The average can of SSB provides about 150 calories, almost all of them from sugar, usually high-fructose corn syrup (e.g., equivalent of 10 teaspoons of table sugar).

In recent years, several studies have examined the association between SSB intake and asthma outcomes, either during pregnancy, childhood or adulthood, and they consistently found that a high consumption of SSB is linked to asthma [24–26]. The exact role SSB in the pathogenesis of asthma is still unclear (e.g., the role of added preservatives or beverages with excess free fructose) [27].

In adults, two cross-sectional studies [28,29] and one longitudinal study [30] have been published regarding the role of SSB on asthma outcomes, and all three reported a positive association. In our opinion, the handling of confounding and effect modification is problematic in most epidemiological studies of the diet-asthma association. Indeed, given the established evidence that links SSB to obesity and that links obesity to asthma, it is likely that obesity act as a potential mediator in the SSB–asthma association (and not a confounder). Whereas the analyses performed by Shi et al. and DeChristopher et al. were adjusted for obesity [28,30], Park et al. performed a stratified analysis for obesity and, interestingly, reported that frequent SSB consumption was associated with current asthma among non-obese adults only [29]. Other conditions could also lie in the causal pathway between SSB intake and asthma symptoms, such as gastroesophageal reflux disease (GERD) which is closely associated with SSB intake [31] and greater asthma symptoms [32], but can also exhibit complex temporal association with obesity. We encourage more studies using modern approaches to causal inference which offer a framework to better address these issues [16].

4. Conclusion

In the context of preventing chronic diseases, public health initiatives to improve respiratory health through dietary advice are particularly relevant and timely. However, the impact of deleterious dietary factors, as reflected by the Western diet, in the etiology of specific asthma phenotypes remains unclear. Recent studies lent further support to the potential deleterious effect of processed meat intake in asthma, and more studies are needed regarding other novel dietary factors (such as SSB). We encourage studies with better asthma phenotyping and that better account for obesity as a potential mediator of diet-asthma associations.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

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.