# Diet and Asthma: A Narrative Review
## 2 Asthma Phenotypes and Endotypes
The principal cytokines involved in this endotype are IL-6, IL-8, and IL-17 [11], mainly produced by the Th-17 response [7], causing neutrophific infiltration and AHR [14]. The Th-1 pathway is responsible for elevated interferon-\(\gamma\) (IFN-\(\gamma\)) and tumor necrosis alpha (TNF-\(\alpha\)) levels [7,14]. A visual representation of T2H and T2L asthma and the involved cytokines are presented in Figure 1.  
Within T2H and T2L endotypes there are also varying phenotypes. Inside the T2H endotype: atopic, late onset, and aspirin-exacerbated asthma; Inside the T2L endotype: non-atopic, smoke-related, obesity-related, and elderly asthma. All of these phenotypes manifest with typical symptoms ranging from wheezing and shortness of breath, to coughing and chest tightness, and are accompanied by variable airflow obstruction [9]. Patients with T2L asthma typically respond poorly to corticosteroids and may therefore be challenging to treat [15]. A substantial body of evidence has documented the co-occurrence of asthma and obesity, implying that the pathobiology of these conditions may be linked [5,16,17,18,19,20,21]. Obesity and asthma have increased dramatically over the last decades [5,19,21,22,20], and have become two of the most common and challenging health issues worldwide [19,21]. According to recent reports of the Global Burden of Disease Study, a high body mass index (BMI) is believed to be one of the most important risk factors for asthma [23,24]. Obesity-mediated asthma has a more severe phenotype [7,25], with obesity seeming to increase asthma prevalence and incidence as a disease modifier, thereby making it more challenging to control [5,25,26,27]. Individuals with this phenotype present worse asthma symptoms and  
Figure 1: T2-high and T2-low asthma and their involved lymphocytes and cytokines. Th, T helper lymphocytes; ILCs, innate lymphoid cells; and IL, interleukin. a lower quality of life [5; 7]. Obesity-mediated asthma appears to be mediated by non-T2 mechanisms, with lower levels of fractional exhaled nitric oxide (FeNO) and normal blood eosinophils [7]. Changes in DNA methylation may influence the Th-1 polarization seen in obesity-mediated asthma, suggesting that environmental factors may contribute to the disease phenotype [17]. It was observed that obese mice presented a higher airway hyperresponsiveness compared to non-obese mice [28]. The diverse mechanisms underlying the asthma-obesity phenotype may be linked to mechanical impediment, hormonal influence, inflammation [5; 14; 29], diet [5; 30], metabolic dysregulation, and genetic and immune factors [5; 29]. Deposition of adipose tissue in the area of the abdomen and chest seems to raise abdominal pressure resulting in an increase of airway resistance and residual capacity over time and in a decrease in tidal volume and airway caliber [14; 29; 31]. These mechanical changes appear to be contributing to bronchial remodeling, increasing airway obstruction and hyperresponsiveness, and thus the risk of asthma [29]. Adipose tissue is an endocrine organ that produces hormones that can influence both inflammation and metabolism. Fat accumulation results in elevated serum concentrations of leptin and decreased levels of adiponectin [14; 27]. The increase in leptin production by the adipose tissue may have a proinflammatory effect by inducing neutrophil chemotaxis, the production of reactive oxygen species (ROS), the activation of natural killer cells and macrophages, and the production of Th-1 cytokines such as IL-6 and IFN-\(\gamma\)[14]. On the other hand, adiponectin inhibits the effects of proinflammatory cytokines on endothelial and other cell types, such as TNF-\(\alpha\) and IL-6, while also inducing the expression of anti-inflammatory cytokines (IL-10 and IL-1 receptor antagonists) [32]. Obesity-promoting diets, such as the Western diet pattern, are typically high in saturated fatty acids and low in dietary fiber and antioxidants. There is a growing body of evidence on the negative effects of these unhealthy diets on asthma [3; 5].