Octavio Galindo, MD, pediatric allergist from Clínica Universidad de Navarra.

Octavio Galindo, MD

New prospective data from the SENDO cohort suggest that ultra-processed food (UPF) consumption may be a meaningful modifiable risk factor for childhood 

The study followed 691 Spanish children aged 4 to years for a mean of 3.4 years and found that those consuming more than 30% of total energy intake from UPFs had a nearly 4-fold greater risk of developing asthma compared with peers in the lowest consumption tertile (hazard ratio [HR], 3.76; 95% CI 1.15–11.51; 

 =.02). The adjusted risk for asthma in each tertile of UPF consumption was 2.6% for T1, 9.9% for T2, and 7.6% for T3 (

 =.03). No significant association was observed for allergic asthma, atopic dermatitis, aeroallergen sensitization, or food allergy, suggesting the mechanism may operate through non-atopic inflammatory pathways rather than classic IgE-mediated sensitization.

UPFs, classified as NOVA Group 4 foods, are industrially formulated products containing ingredients not typically used in home cooking, such as artificial flavors, emulsifiers, and preservatives. The investigators propose that advanced glycation end-products (AGEs), formed when these foods are processed under high heat and low humidity, may underlie the UPF-asthma link. AGEs bind to RAGE, a receptor highly expressed in lung tissue, activating Toll-like receptor 4 and the NF-kB pathway.2 This triggers the release of pro-inflammatory cytokines, including IL-6 and IL-8, promoting airway hyperresponsiveness independent of IgE-mediated mechanisms.3

spoke with first author Octavio Galindo, MD, pediatric allergist from Clínica Universidad de Navarra in Spain, about what drove the investigation, how clinicians should interpret the magnitude of the findings, and what families should know about UPF intake in early childhood.

What led you to investigate ultra-processed food consumption as a potential risk factor for asthma in children?

 For the last 20 or 30 years, there has been interest in research looking at all the factors that could work as risk factors [for] asthma and allergic diseases. We understand the genetic [factors] and all the factors… around children that could increase the [risk of] asthma in childhood, but we are not very clear [on] what the power of each of these factors’ [is].

Ultra-processed food [consumption] has been increasing for the last 30 years and [is now] part of our daily [lives] in our industrialized world. [Understanding whether] the ultra-processed food [is an additive risk factor]—to really understand the whole image of [the] epigenetics [of] asthma—is one of the most important things we have been [working toward] for the last 20 years.

Your results suggest a nearly fourfold increased risk of asthma in children with higher ultra-processed food intake. How should clinicians interpret the magnitude of this finding?

 That's…amazing. Even my research group was amazed about the increase, the almost 4-fold [association of] ultra-processed food [with asthma].

What I do on [a] normal daily basis is understand the risk factors that could increase the probability that a child [will develop] a specialized phenotype of asthma. We understand all about [increased hospitalization], infections, viral infections, [emergency visits], the need [for] beta-2 agonists, but we haven’t [fully understood the role of] diet.

Understanding that [consuming] over 30% of daily [intake from] ultra-processed food can increase… the risk of asthma in children [by almost 4 times] is a very important factor—[one we need] to ask families about on [a] daily basis.

The association was specific to asthma and was not seen for atopic outcomes like aeroallergen sensitization or food allergy. What does that suggest about the underlying mechanisms?

 We were looking for association[s] [with] food allergy, atopic dermatitis, and allergic sensitization. The [field has worked] to understand or put [into] a wider [perspective] the mechanism[s] which we all understand — the [Gell and Coombs] classification, which is type 1, 2, 3, and 4 hypersensitivity. [In] the position paper of the [EAACI] that was published 2 or 3 years ago, they [added] the number 5, which is all about the epithelial barrier alteration, and that's the [physiological] mechanism that we are trying to understand about the asthma.

The problem is that we haven't found an association [between] the ultra-processed food [and] the allergic disease. We have understood that with asthma, the mechanism behind it is that the ultra-consistent foods produce what is called the advanced glycation products," which, normally, when they are absorbed into our organism, go directly to [their specific] receptor [for advanced glycation end-products]. [This can] increase pro-inflammatory signals [including] interleukin-6, interleukin-8, and tumor necrosis factor.

How do you address concerns about residual confounding or dietary measurement error in interpreting these results?

 What we try to understand first is the statistical models that we have to use. First, we start a linear regression and a logistic regression to understand the association between UPS and asthma.

, you can see the confounders we have put into the models. Even [after accounting for] those factors, the association still persists between UPF and asthma. One very important confounder is obesity… [or] weight status, [which maintains] the effect of asthma and the consumption of ultra-processed food in the higher percentile or tertiles of consumption. It means that [weight status] is not only a mediator [but also a co-factor that does not] decrease the effect of the association.

From a practical standpoint, what should clinicians take away regarding ultra-processed food consumption in early childhood?

 In our daily practices, especially in asthma clinics, it's very important to look [at] all the co-factors or the risk factors that could increase the probability of... [an] asthma phenotype. We are trying to understand what the waste of each of these factors is, for example, the smoking status of their parents [and] their smoking exposure.

If we can understand the conception of ultra-sensitive food, we can ask our patients in a very easy way through a [daily food] questionnaire and see if there is a consumption of over 30% of ultra-processed food. We will encourage our patients to decrease [ultra-processed food consumption] to decrease their probability of having asthma or maintaining an asthma phenotype in late childhood.

Is there anything else you'd like to highlight about this study?

 It's very important [for] pediatricians and pediatric allergists and everyone [who works with children] to increase the awareness of the risk of ultra-processed food—not only for asthma but for other non-communicable diseases that have been described as a potential [contributing] factor.

Galindo O, Goikoetxea MJ, Moreno-Galarraga L, et al. Ultra-Processed Food Consumption and Childhood Allergic Diseases: Increased Risk of Asthma Onset in the SENDO Project. 

Perkins TN, Donnell ML, Oury TD. The axis of the receptor for advanced glycation endproducts in asthma and allergic airway disease. 

. 2021;76(5):1350-1366. doi:10.1111/all.14600

Skurk T, van Harmelen V, Hauner H. Angiotensin II Stimulates the Release of Interleukin-6 and Interleukin-8 From Cultured Human Adipocytes by Activation of NF-κB. 

Arteriosclerosis, Thrombosis, and Vascular Biology

. 2004;24(7):1199-1203. doi:https://doi.org/10.1161/01.atv.0000131266.38312.2e

Articles

Octavio Galindo, MD, discusses findings from a prospective Spanish cohort (SENDO) linking high UPF intake to asthma incidence in school-age children.